The CDC transmission rates are surely below the average real-world HIV transmission rate (due to the nature of the European study sample),
I would have given more creedence to this view at the beginning of this whole inquiry, but in another branch several other posters found some large meta-analysis studies, and low and behold they confirm and agree with the old CDC European study. I discuss that here
Of note is that the infection rate in 1st world countires agrees with the original CDC European Study, and the infection rate in Africa/3rd world appears to be 3-6 times higher. Metastudies which mix 1st and 3rd world results get rates somewhere in between.
Some of these metastudies were of thousands of individual studies, and say what we will about them, I think they nail down the real world transmission rates, and the 1st world rates are just as low as I originally quoted (or lower)
and there are features of the data that are easier to explain if we acknowledge that HIV’s sexually transmitted: the condom-using couples had lower HIV transmission rates than the non-condom users, men who (claimed to have) had period sex with HIV+ women were at higher risk of transmission than men who (claimed to have) avoided period sex, and so forth. So I continue to disagree that the HIV-is-an-STI view is “obviously bogus according to the orthodox’s own data”.
Effects like this surely can increase transmission rates in specific instances, but for epidemilogical modelling we are interested in the average rates—and note as I analyzed elsewhere, the original CDC European study does attempt to control for condom use—it intends to show infection rates for unprotected sex. I don’t think you can so easily dismiss all these studies and the work that has gone into computing these transmission rates.
I looked up long-term nonprogressors on Wikipedia (not the most reliable source, but anyway), and it looks like many long-term non-progressors have genetic traits that make them better able to resist HIV, or have a weaker form of HIV.
This is certainly a possibility and fits what we know with viruses—variable genetic resistance is to be expected.
However, what is important is how one samples and when. If you take a sampling of survivors years later, then sure you can expect to be finding survivors due to genetic resistance.
But if you sample a subset based only on the criteria that they refuse medication after testing seropositive, then that is a very different sampling, and you should expect it to be largely uncorrelated from genetic resistance (unless you want to argue that people with genetic resistance are strongly expected to resist medication!, but I hope you won’t take that route)
You do bring up a potentially valid criticism:
I also saw that the group in Germany Duesberg’s talking about all come from Kiel, a relatively small city (population about 240,000). I’m wondering whether the people living there could be more likely to have HIV-resistant genes. Or maybe the form of HIV circulating there is less virulent? (Or both?)
Possibly, but I don’t find a reason why we should expect this without specific evidence—from what I understand the HIV-1 virus variants spread diffusely in specific at-risk subgroups. It would help the case if the study had more widely distributed patients, and maybe there are other such studies, but it isn’t strong evidence against. We can’t expect many patients to have resisted medicating, and those that did would tend to be clustered geographically in regions where some cluster of doctors were allowed to hold that view and resist medication for a long period of time and study the patients. From what I understand, this was not allowed to happen in the states.
You raise some further methodological questions:
The first thing that jumps out at me is the lack of detail. I’m curious about how Koehnlein discovered the subjects for the study (personal contact?) and whether they included all of the eligible patients they found. I also wonder how Koehnlein followed up patients, and how regularly. How rigorously do they track the patients to make sure they’re staying off HIV drugs & illicit drugs? How often do they check on them to see whether they’re still alive? When was the last follow-up?
I don’t know, and yes these are interesting questions, and it would be useful if there was a meta-study of all long-term survivors/non-progressors.
The article’s dated mid-2003, but it looks like Koehnlein’s added no new subjects to the study since 2000, and the latest update is from 2001 (when the 3 dead patients died). It would be very interesting to know how many of the remaining 33 patients are still alive 7-9 years on
Yes, this would be interesting, but note that we shouldn’t expect these people to have full life expectancy, in either theory—as seropositive status is clearly a marker for ill-health. The bigger question is does refusing medication increase lifespan? That is the central point.
Even if they all died after 12 years on average, that still may be better than typical, for example.
I looked for later publications by Koehnlein on his study and didn’t find any (which is a bit of a red flag in itself).
A follow up would be interesting, but lack thereof isn’t necessarily a red-flag. They are going to die at some point, and probably much earlier than seronegatives. The question is one of statistics.
As to your questioning of whether these are “AIDS patients”, I find that is rather irrelevant—we are only concerned with the fact that they tested positive for HIV. If HIV doesn’t strongly cause AIDS, but medication does, then of course we shouldn’t expect these medication refusers to progress into AIDS and become AIDS-patients, which is exactly what the study is showing. So I dont’ understand why you are trying to show that they are not AIDS patients—that’s the whole point! You may be unknowling arguing for the opposition (or perhaps I am confused on your position or you have none).
I would have given more creedence to this view at the beginning of this whole inquiry, but in another branch several other posters found some large meta-analysis studies, and low and behold they confirm and agree with the old CDC European study. I discuss that here
Of note is that the infection rate in 1st world countires agrees with the original CDC European Study, and the infection rate in Africa/3rd world appears to be 3-6 times higher. Metastudies which mix 1st and 3rd world results get rates somewhere in between.
Some of these metastudies were of thousands of individual studies, and say what we will about them, I think they nail down the real world transmission rates, and the 1st world rates are just as low as I originally quoted (or lower)
All of this is consistent with the CDC statistics underestimating the general transmission rate. You write that the rate estimated from the European study “agrees with” meta-analyses of 1st world data, and that the 3rd world rate estimated by meta-analysis is higher still. So pooling the two meta-analytic results gives a global average rate greater than the 1st world average rates, i.e. averages greater than the CDC rates.
and there are features of the data that are easier to explain if we acknowledge that HIV’s sexually transmitted [snip]
Effects like this surely can increase transmission rates in specific instances, but for epidemilogical modelling we are interested in the average rates—and note as I analyzed elsewhere, the original CDC European study does attempt to control for condom use—it intends to show infection rates for unprotected sex. I don’t think you can so easily dismiss all these studies and the work that has gone into computing these transmission rates.
I don’t think I am dismissing these studies and the work. The bit of my comment you’re quoting refers, after all, to secondary analyses in one of those studies. The point I’m trying to make by drawing attention to those analyses isn’t something like “look, the transmission rates are higher if you don’t use condoms, clearly they’re high enough for HIV to spread through the population”, but instead “associations between condom use and transmission rates, and between sex during menses and transmission rates, have a far higher likelihood in a model where HIV is an STI than in a model where it’s not”. It’s much easier for me to explain why having sex with a woman at particular times in her menstrual cycle would correlate with HIV transmission if I presume HIV’s sexually transmitted, which I interpret as evidence for [edited: I had a brain fart and originally wrote “against”] the view that HIV’s an STI.
However, what is important is how one samples and when. If you take a sampling of survivors years later, then sure you can expect to be finding survivors due to genetic resistance.
But if you sample a subset based only on the criteria that they refuse medication after testing seropositive, then that is a very different sampling, and you should expect it to be largely uncorrelated from genetic resistance (unless you want to argue that people with genetic resistance are strongly expected to resist medication!, but I hope you won’t take that route)
Don’t worry, I’m not. I’m suggesting that because the sampled people all come from the same small geographic region, it’s possible that genetic resistance and/or weaker HIV variants are more common among them.
Possibly, but I don’t find a reason why we should expect this without specific evidence—from what I understand the HIV-1 virus variants spread diffusely in specific at-risk subgroups. It would help the case if the study had more widely distributed patients, and maybe there are other such studies, but it isn’t strong evidence against.
The specific evidence I have in mind is the geographic restriction of the sample. A group of people from one place will tend to be more genetically similar than a worldwide sample, and will be more likely to share strains of a disease. I expect HIV-1 variants do spread diffusely in subgroups, but I don’t think that rules out my point. Particular alleles of genes spread throughout humanity, but spatial proximity still correlates with genetic similarity among people. Sure, geographic restriction is hardly strong evidence of these things — a sample of people who live on the same street could quite easily contain just as much variety in genes that affect HIV resistance (or variety in HIV substrains) as a wider sample. But with geographic restrictions, the variance is likely to be less. (Notice also that the sample seems to be relatively racially homogeneous — only one of the 36 cases is described as black. That’s more evidence of less genetic variance, though very weak evidence, as racial groupings don’t represent much genetic variance.)
Yes, this would be interesting, but note that we shouldn’t expect these people to have full life expectancy, in either theory—as seropositive status is clearly a marker for ill-health.
Yes, but you originally presented the study as “data very close to what [I am] proposing”, and part of my proposal was that the study’s subjects “are followed up regularly” for 20+ years. Koehnlein’s study started in 1985, most of the subjects entered it in the 1990s or later, the latest update is from 2001, and the published report is from 2003. So most subjects don’t seem to have had anything like a 20-year (or more) follow-up.
The bigger question is does refusing medication increase lifespan? That is the central point.
The bigger question we’re looking at is whether HIV causes the complex of conditions we recognize as AIDS (and, before that, HIV transmission rates).
Even if they all died after 12 years on average, that still may be better than typical, for example.
True, but the question is how much better than average their lifespan was, and the causes of death also matter. If the patients lived for many post-HIV years more than average, but most of them died of Kaposi’s sarcoma, I would strongly suspect AIDS.
A follow up would be interesting, but lack thereof isn’t necessarily a red-flag.
It doesn’t mean the study is somehow wrong, but I see it as a warning sign. It’s very unusual for someone to spend 16+ years on a unique, systematic study of untreated HIV patients, and then not publish it anywhere except as a one-page summary in the middle of a review article that I suspect was mostly written by someone else. I have a hunch that Koehnlein’s unable to get the study published in full.
As to your questioning of whether these are “AIDS patients”, I find that is rather irrelevant—we are only concerned with the fact that they tested positive for HIV.
I can think of two reasons why it’s very relevant. First off, if most of the subjects didn’t have AIDS, that might well explain why their death rate’s less than that of AIDS patients (and Duesberg & Koehnlein quite explicitly compare the sample’s death rate to that of “German AIDS patients”) — one dies of AIDS instead of HIV per se, and it normally takes years to go from being HIV+ to having AIDS. Secondly, Duesberg & Koehnlein say the study is of “AIDS patients”; if it turns out that there are people in the study who didn’t have AIDS, D&K have made a specious comparison, and a false claim about the nature of the study. That would raise questions about how much I should trust their report of it.
If HIV doesn’t strongly cause AIDS, but medication does, then of course we shouldn’t expect these medication refusers to progress into AIDS and become AIDS-patients,
Agreed, with the proviso that one would have to wait a long time to be sure that HIV didn’t eventually progress to AIDS.
which is exactly what the study is showing.
Disagreed. If you’re agreeing with my suspicion that some of the people in Koehnlein’s study didn’t have AIDS, you’re implicitly accepting my guess that the clinic symptoms and CD4 counts in the table are those observed for each subject when they entered the study, because that forms the basis for my suspicion. And if you believe that, it follows that you can only infer whether a subject had AIDS when they entered the study, and not whether they later developed AIDS.
So I dont’ understand why you are trying to show that they are not AIDS patients—that’s the whole point! You may be unknowling arguing for the opposition (or perhaps I am confused on your position or you have none).
So pooling the two meta-analytic results gives a global average rate greater than the 1st world average rates, i.e. averages greater than the CDC rates.
For a variety of reasons, I find it useful to separate the two, and the 1st world rates are the most important—the virus outbreak started in San Francisco essentially (following the end tail of the massive hippie/drug liberation social experiment). Also, the 3rd world rates are suspect in general, as one of the meta-studies notes, for a variety of reasons. And regardless, even the 3rd world rates are 30 times lower than typical STD’s, even if they were accurate (which is dubious).
The specific evidence I have in mind is the geographic restriction of the sample.
Yes, but as you admit,
Sure, geographic restriction is hardly strong evidence
So at this point I think it is more time profitable to switch gears and spend a little effort investigating other LTP reports other than this single study. And just a little google searching shows that there appears to be now a number of other LTPs from across the world that are similar to the Koehnlein group—and avoiding traditional treatment appears to be a common link. You can google it as well, but here are some links:
from an article in Health Care Industry (older − 2000):
An adjunct to immune-based research has been the close study, since the early 1990s, of HIV-infected individuals who have not progressed to AIDS in 10 or more years and who have not taken antiretroviral therapy
It has been 16 years since Brothers learned he was HIV-positive.
Since then, he has never taken AIDS drugs or had any illnesses associated with the disease. Despite his good fortune, Brothers says he feels isolated.
And finally here is a compilation of another dozen studies or cases of untreated LTNPs (older hasn’t been updated recently)
So it doesn’t look like the Koenhnlein study is an isolated incident. I am still looking for more recent studies or follow ups.
From everything I know so far, the vast majority of patients were treated, so if treatment has a beneficial effect at all, then it follows that the ratio of treated LTNPs to untreated LTNPs must be equal or greater to the original treatment ratio. I understand that in the west that treatment ratio was very high, probably > 95%
And as far as I can tell, we aren’t seeing anything like that ratio in LTNPs, so this could be very strong support indeed for at least part of the Deusberg hypothesis: that the treatment can itself cause the disease.
Edit: I completely guessed on that 95%, and later found this telling quote in the NYT article (I am reading these as I go):
Levy believes that about 5 percent of people with HIV are medicine-free and still healthy after 10 years.
But what it would really need is a big long term study with the sampling precommitted early based only on choice of treatment strategy. Actually, this should be how our entire medical system works in general. If the drug companies produce a treatment like AZT, doctors and patients get to choose treatment strategies, and overall mortality data is collected slowly over time. Survival of the fittest strategy.
which is exactly what the study is showing.
I should have said here “what the study intends to show”
Disagreed. If you’re agreeing with my suspicion that some of the people in Koehnlein’s study didn’t have AIDS, you’re implicitly accepting my guess that the clinic symptoms and CD4 counts in the table are those observed for each subject when they entered the study, because that forms the basis for my suspicion. And if you believe that, it follows that you can only infer whether a subject had AIDS when they entered the study, and not whether they later developed AIDS.
I was under the impression they tested them when they entered the study and then periodically thereafter just as you’d expect. The overall concern is the long term result—the death rate. I thought the entire point Deusberg was making was that overall mortality was lower in this untreated group than in the general treated population, and the medications themselves were actually causing AIDS progression.
For a variety of reasons, I find it useful to separate the two, and the 1st world rates are the most important—the virus outbreak started in San Francisco essentially (following the end tail of the massive hippie/drug liberation social experiment).
As I understand things, HIV jumped into the human population in Africa decades before hippies and the 1960s counterculture, and that only after being established in West/Central Africa did it reach the US. As such, the 3rd world transmission rates have just as big a role to play as 1st world transmission rates. With an external pool of infected people established, it became possible for HIV to be reintroduced to the US over & over again until it landed in US subpopulations that spread it with needle sharing & frequent anal sex.
Also, the 3rd world rates are suspect in general, as one of the meta-studies notes, for a variety of reasons. And regardless, even the 3rd world rates are 30 times lower than typical STD’s, even if they were accurate (which is dubious).
Without being more specific about what’s wrong with the rates, I’m not sure why this means the 3rd world rates are necessarily about equal to (or less than) the 1st world rates. At any rate, HIV is not a “typical STD”, and a lower transmission rate than other STDs doesn’t mean much as long as HIV’s rates are sufficient to enable its spread. Also, Wei_Dai suggested that the P/V sexual transmission rate for HIV is comparable to that of genital herpes, a point you didn’t seem to dispute in your reply. Do you believe that genital herpes has too low a transmission rate to be an STD?
So at this point I think it is more time profitable to switch gears and spend a little effort investigating other LTP reports other than this single study. And just a little google searching shows that there appears to be now a number of other LTPs from across the world that are similar to the Koehnlein group—and avoiding traditional treatment appears to be a common link.
But here’s the thing: the lone fact that a case report or study has some LTNPs doesn’t necessarily mean much in terms of questioning the HIV-AIDS link. For example, the studies in the 2000 Research Initiative/Treatment Action! article (I think “Health Care Industry” is just the name of the section on findarticles.com where the article’s mirrored) seem to focus on gathering together people already known to be treatment-refusing LTNPs, and finding out what makes them LNTPs. Simply observing that treatment-refusing LTNPs exist doesn’t convince me. Even if 99% of HIV+ people progress to AIDS within some time frame, with so many HIV+ people there are going to be a lucky few who turn out to be treatment-refusing non-progressors.
By contrast, Koehnlein’s methodology seemed to be different, which was why I initially thought that work might be compelling. I’d assumed that Koehnlein systematically recruited people into the study when they originally tested HIV+, not later, which would prevent Koehnlein gaming the study by excluding non-LTNPs. (Of course, with all the questions I now have about the study, I’m questioning even that. D&K don’t say when the subjects were recruited into the study, only when they were diagnosed HIV+. Possibly Koehnlein recruited subjects years after their HIV+ diagnoses.)
And finally here is a compilation of another dozen studies or cases of untreated LTNPs (older hasn’t been updated recently)
The catch with those 14 reports (the last of which is just a second-hand anecdote) is the same as for the other ones you linked: the page listing them doesn’t say what their sampling strategies were, and I think it’s likely that a lot of the reports’ authors deliberately sought out treatment-refusing LTNPs instead of representative samples. (The list is probably also a selective one, considering the website hosting it.) For example, the first report in the list is “based on 10 HIV+ people” who didn’t use antiviral drugs. I find it unlikely that doctors would bother publishing a study of only 10 LTNPs if those people had taken antiviral medication; it wouldn’t be very informative. It’d effectively be a tiny drug trial, and there are already far bigger trials of anti-HIV drugs. So I’d guess the doctors’ aim was to deliberately search for as many treatment-refusing LTNPs as they could find, because other doctors have something to learn from how their bodies work. If so, it wouldn’t be surprising that they found a handful.
From everything I know so far, the vast majority of patients were treated, so if treatment has a beneficial effect at all, then it follows that the ratio of treated LTNPs to untreated LTNPs must be equal or greater to the original treatment ratio.
That only follows if there aren’t any confounding factors associated with treatment status. If (making up an example here) HIV+ people being treated use treatment as an excuse to resume risky behaviour, and the treatment is only marginally effective, we might well end up with relatively few treated LTNPs. (I haven’t looked into this. Maybe it turns out that there aren’t any major confounding factors, but I wouldn’t want to assume them away without evidence.)
And as far as I can tell, we aren’t seeing anything like that ratio in LTNPs, so this could be very strong support indeed for at least part of the Deusberg hypothesis: that the treatment can itself cause the disease.
If you’re basing this on counting reports of LTNPs, you might be getting a skewed picture, since treatment-refusing LTNPs are much more newsworthy than LTNPs who accept treatment, and the latter probably don’t get so many of their own journal articles and magazine profiles. To count them, you’d probably have to locate reports of HIV drug trials that happen to have data on how the testees progress.
Edit: I completely guessed on that 95%, and later found this telling quote in the NYT article (I am reading these as I go):
Levy believes that about 5 percent of people with HIV are medicine-free and still healthy after 10 years.
It usually takes several years for HIV to progress with AIDS, with or without treatment. So it wouldn’t be that surprising if there’s a large minority of people who don’t develop AIDS within a decade of HIV infection, and a fair few of them are probably, yes, medicine-free. (Plus, of course, we’re looking at a newspaper’s paraphrase of something a scientist said, so I’m inclined to exercise caution.)
I should have said here “what the study intends to show”
I was under the impression they tested them when they entered the study and then periodically thereafter just as you’d expect. The overall concern is the long term result—the death rate. I thought the entire point Deusberg was making was that overall mortality was lower in this untreated group than in the general treated population, and the medications themselves were actually causing AIDS progression.
To be honest, I think D&K are confused themselves about what the study’s meant to show. D&K call it “a study of AIDS patients”, but then they write “our relatively small sample supports the hypothesis that without anti-HIV drugs and/or recreational drugs HIV fails to cause AIDS.” But if the subjects were all AIDS patients, how could the study show that they failed to progress to AIDS? They would already have had AIDS!
If you’re correct that Duesberg’s intent was to make the point “that overall mortality was lower in this untreated group than in the general treated population, and the medications themselves were actually causing AIDS progression”, then he’s trying to have it both ways. He can’t infer the first thing (lower mortality) unless the study subjects are AIDS patients, because other AIDS patients are his comparison group, and he can’t infer the second thing (medications causing AIDS) unless some of the subjects aren’t AIDS patients.
Also, I doubt Koehnlein did systematically test the subjects periodically for AIDS. CD4 counts are missing for some of the asymptomatic patients, and to test them for AIDS, they would have needed CD4 counts. So either Koehnlein didn’t have their CD4 counts (which implies that Koehnlein wasn’t periodically testing them for AIDS), or Koehnlein’s selectively withholding CD4 counts (and something funny’s going on).
Whew. The more I go over this study, the more worrying it gets.
Ah, unfortunately this got too long, so I had to split it.
To be honest, I think D&K are confused themselves about what the study’s meant to show. D&K call it “a study of AIDS patients”, but then they write “our relatively small sample supports the hypothesis that without anti-HIV drugs and/or recreational drugs HIV fails to cause AIDS.” But if the subjects were all AIDS patients, how could the study show that they failed to progress to AIDS? They would already have had AIDS!
I think this was a confusion of terminology, and “AIDS patient” in the general sense was used to just refer to all HIV+ patients he was treating. It did not refer to only a subset that had later stage ‘AIDS’ symptoms. At least, that’s how it read to me.
From what I understand, Koehnlein somehow found a way to treat patients without antivirals legally, so patients seeking non-antiviral treatment came to him. His ‘study’ is just a record of all such patients, when they first came under his care, their backgrounds, and eventual prognosis (a couple of deaths out of thirty or so patients so far).,
Also, I doubt Koehnlein did systematically test the subjects periodically for AIDS. CD4 counts are missing for some of the asymptomatic patients, and to test them for AIDS, they would have needed CD4 counts. So either Koehnlein didn’t have their CD4 counts (which implies that Koehnlein wasn’t periodically testing them for AIDS), or Koehnlein’s selectively withholding CD4 counts (and something funny’s going on).
Koehnlein may subscribe to the Duesberg hypothesis, and as such wouldn’t place any special value on persistent tracking of CD4 counts.
Ah, unfortunately this got too long, so I had to split it.
It might be for the best! This splits the Koehnlein study discussion and the general HIV discussion into their own separate subthreads.
I think this was a confusion of terminology, and “AIDS patient” in the general sense was used to just refer to all HIV+ patients he was treating. It did not refer to only a subset that had later stage ‘AIDS’ symptoms. At least, that’s how it read to me.
Yes, we initially read the phrase differently. I originally interpreted it at face value, figuring that in a review article about HIV & AIDS, D&K would take care to avoid confusing having AIDS with being HIV+. I now think I might’ve given them too much credit.
Nonetheless, at one point, D&K must be using “AIDS patients” with its narrow meaning (patients with AIDS proper) and not its informal one (patients with HIV who may or may not also have AIDS), because the statistics they quote for German AIDS patients match the Robert Koch Institut’s AIDS statistics, but not the organization’s HIV+ headcount.
Whatever D&K’s intentions or confusions, my earlier point that the study can’t provide strong, simultaneous support of all the conclusions drawn from it still stands.
Koehnlein may subscribe to the Duesberg hypothesis, and as such wouldn’t place any special value on persistent tracking of CD4 counts.
If so, Koehnlein’s testing his (her?) own definition of AIDS, not an orthodox one, and all bets are off.
As I understand things, HIV jumped into the human population in Africa decades before hippies and the 1960s counterculture, and that only after being established in West/Central Africa did it reach the US. As such, the 3rd world transmission rates have just as big a role to play as 1st world transmission rates. With an external pool of infected people established, it became possible for HIV to be reintroduced to the US over & over again until it landed in US subpopulations that spread it with needle sharing & frequent anal sex.
That’s a theory, but it has some critical flaws. Namely one must wonder why did it not spread via prostitutes, needle sharers and blood transfusions earlier? Condom use dropped with the adoption of the pill in the 1960′s and the sexual liberation opened up a hetero transmission channel which has about the same net transmission rate (always limited by the insertive step).
AIDS became an epidemic in San Francisco in the early 80′s, and it grew quickly from a handful of cases to effect a large portion of the gay population, and was closely correlated with a diverse number of fundamental lifestyle differences. It is this phenomena, this quick sudden outbreak in a very specific subgroup, which I find extremely difficult to reconcile with the transmission data. Tops and bottoms tend to specialize so the rate-limiting factor for expansion in the gay community would be closer to the insertive A rate, at around 0.06% vs receptive at 0.5%. Needle sharing is about 10 times more effective, and blood transfusion is around 1,000 times more effective.
But all the early cases are in this one specific group, which is not even the highest risk group. I mean, the transmission rates for insertive V and A are about the same, and there are far more heteros than homos, so it just doesn’t make any sense. And don’t tell me the homos are having all the sex—they may be having more individually, but not when considering prostitutes and sexually liberated women in the 60′s and 70′s, the fact that heteros have anal as well, and the 100 to 1 hetero to homo ratio. The overall hetero transmission channel is much much larger, especially after considering needle sharing and transfusions, and yet the disease only appears in the homo subgroup, time and time again. Why?
Ignore for a second all high level conceptions about HIV. Don’t privilege the orthodox HIV hypothesis, instead compartmentalize and consider just this evidence concerning transmission rates, and how that evidence should cause one to update from an initial 50⁄50 split between two alternate hypotheses:
HIV spreads primarily horizontally and is novel in homo sapiens
HIV spreads primarily vertically and has been in homo sapiens for a long time
The transmission rates clearly favor 2 - the virus can barely spread sexually, but can spread fairly easily antenatally.
Also, if you actually read into the depths of these studies, it becomes clear that there is a strong framing bias to favor the default sexual transmission theory. The actual sexual transmission rates are not known with certainty, and all of these studies depend on the orthodox HIV model. The actual horizontal transmission rate may be . .. zero.
One of the more interesting hetero sero-discordant studies is the Padian 10 year study. Trying to isolate for hetero sexual transmission, they actually strictly eliminated all drug users by using actual drug tests—something that others have not done to my knowledge. They then did the typical questionnaire analysis trying to determine how each seropositive index member in the couple actually caught HIV—which is more or less just a random guessing game, and then they applied regression techniques to look for risk factors.
The risk factors they found are more or less random, and do not point to a sexually transmitted disease. For instance:
We found only marginal significance
for enrollment in the study prior to 1990 (OR = 1.9),
not using condoms (OR = 1.7), and >300 unprotected
penile-vaginal or penile-anal contacts (the median
number of contacts) (OR = 1.6), all of which had been
found to be significant in previous analyses (2, 6, 14).
So large amounts of unprotected sex did not appear to be a very significant risk factor. The highest risk factor was just anal sex as a practice, not the number of contacts.
But what was really interesting in this group of some 600ish hetero non-drug users was that during the length of the study, there was not a single seroconversion, even though condom use in these couples was imperfect:
We observed no seroconversions after entry into the study. [ ] Nevertheless,
only 75 percent reported consistent condom
use in the 6 months prior to their final follow-up visit.
Forty-seven couples who remained in follow-up for 3
months to 6 years used condoms intermittently, and no
seroconversions occurred among exposed partners.
There is zero evidence that non-drug using heterosexuals acquire the disease sexually, and studies such as this are evidence favoring a vertically transmitted virus.
At any rate, HIV is not a “typical STD”, and a lower transmission rate than other STDs doesn’t mean much as long as HIV’s rates are sufficient to enable its spread.
Why does it only spread laterally into gay men and drug users, even though this is extraordinarily unlikely if it truly is horizontally transmitted?
Also, Wei_Dai suggested that the P/V sexual transmission rate for HIV is comparable to that of genital herpes, a point you didn’t seem to dispute in your reply. Do you believe that genital herpes has too low a transmission rate to be an STD?
I haven’t analyzed genital herpes and know very little about it, and regardless it is irrelevant. If the data says that HIV can not be sexually transmitted, and another disease has the same epidemologial data and is also called an STD, that somehow doesn’t magically change the data. It just makes both classifications wrong.
Simply observing that treatment-refusing LTNPs exist doesn’t convince me. Even if 99% of HIV+ people progress to AIDS within some time frame, with so many HIV+ people there are going to be a lucky few who turn out to be treatment-refusing non-progressors.
There is no ‘luck’ and it all depends on the ratios. If only 1% of HIV+ people refuse treatment, but even just 10% of all “long-term non progressors” refuse treatment, then clearly treatment itself is part of the problem.
From everything I know so far, the vast majority of patients were treated, so if treatment has a beneficial effect at all, then it follows that the ratio of treated LTNPs to untreated LTNPs must be equal or greater to the original treatment ratio.
That only follows if there aren’t any confounding factors associated with treatment status. If (making up an example here) HIV+ people being treated use treatment as an excuse to resume risky behaviour, and the treatment is only marginally effective, we might well end up with relatively few treated LTNPs. (I haven’t looked into this. Maybe it turns out that there aren’t any major confounding factors, but I wouldn’t want to assume them away without evidence.)
It is strange and interesting that you think the cofactors only could work in favor of your privileged hypothesis. There is also the placebo effect to consider, and in a drug trial that is not double blind (as the AZT trials could not be) those who found out they were getting placebo believed they were going to die, and that encouraged wreckless behavior, not the other way around. Also, all the reports on LTNPs I have read are unanimous on lifestyle change being a distinguishing factor- reduction in drug use and bathouse type partying, general increase in healthier behavior. However, they still die at accelerated rates, and some eventually get AIDS.
Overall though it is pretty clear that even with some placebo benefit in it’s favor, AZT had no net benefit. If one could factor in the placebo bias, I expect it actually increases mortality a little on the whole. However, the data on the original AZT trial and later the more extensive concorde trial show that AZT has little effect or a small net negative effect. I think it is difficult to pin all of the modern deaths on AZT, and clearly AZT was not the main killer during the trials, but the fact of the matter is we simply do not have a control group to compare to in the long term.
This is the first cohort to basically be on sustained chemotherapy for life. It’s hard to imagine that this could not have negative long term effects.
That’s a theory, but it has some critical flaws. Namely one must wonder why did it not spread via prostitutes, needle sharers and blood transfusions earlier?
I’m not sure which specific time period you’re referring to with “earlier”. If you’re talking about the 1970s, I’d guess it’s because HIV simply hadn’t been introduced to those subpopulations often/early enough to stick. If you’re talking about the early 1980s, well, it looks like HIV did spread, at least among needle sharers and people who had blood transfusions. (I haven’t seen data on prostitutes.) According to this 1985 Science article, 12,932 AIDS sufferers were reported to the CDC by August 30, 1985. 1.5% of them had received blood transfusions within 5 years of diagnosis, and 17% were heterosexuals who’d used IV drugs. (Also, 12% of the homosexual & bisexual men diagnosed were IV drug users.)
It is this phenomena, this quick sudden outbreak in a very specific subgroup, which I find extremely difficult to reconcile with the transmission data. Tops and bottoms tend to specialize so the rate-limiting factor for expansion in the gay community would be closer to the insertive A rate, at around 0.06% vs receptive at 0.5%.
Although I’m sure tops & bottoms “tend to specialize”, I doubt men with dozens of sexual partners are completely picky about which role they play. If men are inconsistent about being the top/bottom, the insertive anal transmission rate is going to be an underestimate. In fact, it’s likely to be an underestimate twice over, because preexisting STIs make transmission more likely, and promiscuous men will have more STIs on average. You’ve also got the handful of IV drug users among these men. If I’d had to bet on where HIV would rear its head first, the bathhouse subculture would’ve been a great choice to put my money on.
Needle sharing is about 10 times more effective, and blood transfusion is around 1,000 times more effective.
But neither of those can have an impact until HIV’s introduced to the subpopulations of needle sharers/blood donors, and even after that, their effect will depend on when HIV reached those subgroups, and how many people in those subgroups start off with HIV.
But all the early cases are in this one specific group, which is not even the highest risk group.
Only if you define “early” as really early: the first reports of IV drug users with AIDS came out in the same year as the first reports of AIDS in gay men. And again, risk isn’t everything. Even if group X has much higher transmission risks than group Y, if the virus reaches group Y first, the earliest infections are likely to emerge in group Y.
I mean, the transmission rates for insertive V and A are about the same,
While the receptive A rate is higher than the receptive V rate.
and there are far more heteros than homos, so it just doesn’t make any sense.
Ease of person-to-person transmission within a subgroup matters more to how quickly a disease spreads through that subgroup than the subgroup’s absolute size.
And don’t tell me the homos are having all the sex—they may be having more individually,
Which increases the ease of transmission.
but not when considering prostitutes and sexually liberated women in the 60′s and 70′s,
Which doesn’t much matter if there’s hardly any HIV among those women to start off with. I’d also guess that the proportion of “sexually liberated women” having as much sex and injecting as much drugs as gay men in the 1970s/1980s bathhouse culture is relatively small.
the fact that heteros have anal as well
As often as promiscuous gay men?
and the 100 to 1 hetero to homo ratio.
See above about subpopulation size.
The overall hetero transmission channel is much much larger, especially after considering needle sharing and transfusions, and yet the disease only appears in the homo subgroup, time and time again. Why?
To extend your own metaphor, the “hetero” channel was wider than the “homo” channel, but the “homo” channel had faster flow. Plus, again, there were gay men who engaged in IV drug use, and if gay men were among the first US citizens exposed to HIV, as is very possible, that would’ve given them a head start.
Ignore for a second all high level conceptions about HIV.
Not sure what that means specifically.
Don’t privilege the orthodox HIV hypothesis,
It’s the hypothesis favoured by the medical establishment and the scientific mainstream on the basis of evidence that is at least circumstantial, and at best definitive, which suggests it’s a good starting point. I’m not plucking an arbitrary hypothesis to defend out of thin air.
instead compartmentalize and consider just this evidence concerning transmission rates, and how that evidence should cause one to update from an initial 50⁄50 split between two alternate hypotheses:
HIV spreads primarily horizontally and is novel in homo sapiens
HIV spreads primarily vertically and has been in homo sapiens for a long time
The transmission rates clearly favor 2 - the virus can barely spread sexually, but can spread fairly easily antenatally.
I really disagree with how you’re framing things here. It’s screwy to split horizontal transmission & vertical transmission into separate hypotheses, since both processes are happening right now throughout the human race, and both processes happen at different rates across time & place. I don’t understand why the mode of transmission corresponds to how long HIV’s been circulating in humanity, either.
Mother-child HIV transmission rates per child (without anti-HIV prophylaxis) are generally higher than sexual transmission rates per sex act, sure. But there’re a lot more sexual acts happening than childbirths. So there’s more to the situation than raw transmission rates.
That’s a theory, but it has some critical flaws. Namely one must wonder why did it not spread via prostitutes, needle sharers and blood transfusions earlier?
I’m not sure which specific time period you’re referring to with “earlier”. If you’re talking about the 1970s, I’d guess it’s because HIV simply hadn’t been introduced to those subpopulations often/early enough to stick.
There are several documented cases of early AIDS where we have stored tissue that later tested positive for HIV, such as the gay teenager who died in St Louis in 1969. This poses a serious problem for the standard theories that HIV is transmitted horizontally (unlike any other retroviruses) and presumably came out of Africa. So how did it get into this teenager? You would need some world travelling gay subculture at the time to link the disease to Africa, but not a big enough subculture to create an epidemic. Since only a small portion of men are gay, we should expect that if it came out of Africa the first vectors would have been heterosexual, not homosexual. And as there are several of these strange early cases, it would have had to come over from Africa multiple times, but always only in gay men. This theory is just not salvageable.
Also, consider that the different genetic subtypes are closely associated with particular risk groups—subtype M appears in MSM and IV drug users but not others, which doesn’t make any sense for a horizontally transmitted viral vector. Most of the subtypes are linked to particular geographical regions in Africa, which points to a long history in humans (with M representing a novelty linked to novel behaviour).
Also consider that all other primates have naturally occurring lentivirus family retroviruses very similar to HIV. Consider that the entire family of retroviruses are more symbionts than parasites—humans are ‘infected’ with thousands of different retroviruses, many of which are integrated into our genome, and they have functional roles in gene expression and even the formation of the placenta.
So if all other primates have naturally occurring lentiviruses, why don’t humans? There is a clear evolutionary niche for a lentivirus in mammals, and it seems odd that homo sapiens somehow lost their naturally occurring lentivirus at some point in our evolutionary divergence, only to re-acquire it very recently in the last one hundred years. It just doesn’t make any sense at all.
Retroviruses generally are not horizontally transmittable, and there is no evidence that HIV is an exception. The Padian study in the other thread branch directly shows that HIV is probably not sexually transmittable.
There are several documented cases of early AIDS where we have stored tissue that later tested positive for HIV, such as the gay teenager who died in St Louis in 1969. This poses a serious problem for the standard theories that HIV is transmitted horizontally (unlike any other retroviruses) and presumably came out of Africa.
But most of the earliest confirmed AIDS cases were retracted (David Carr) or have a direct connection to Africa (anonymous Congolese adults & Arvid Noe). It’s only Robert R. (the “gay teenager” you refer to) who didn’t have a direct African connection, but that doesn’t mean there wasn’t one, and such a connection wouldn’t even be necessary with Haiti available as a closer source of HIV.
So how did it get into this teenager? You would need some world travelling gay subculture at the time to link the disease to Africa, but not a big enough subculture to create an epidemic.
This is one teenager. He only had to be unlucky once when having sex with just one infected man.
Since only a small portion of men are gay, we should expect that if it came out of Africa the first vectors would have been heterosexual, not homosexual.
I’m confused. This PNAS paper presents good phylogenetic evidence that the HIV strains causing the North American epidemic came from Haiti, and that Haiti’s HIV came from Africa in the 1960s, which “suggests its arrival in Haiti may have occurred with the return of one of the many Haitian professionals who worked in the newly independent Congo in the 1960s”. So it’s Haitian economic migrants who would’ve been the “first vectors” to carry HIV out of Africa in any real number, and I have no reason to think they were disproportionately homosexual.
And as there are several of these strange early cases,
If by “strange” you mean that all those cases are inexplicable, I disagree.
it would have had to come over from Africa multiple times, but always only in gay men.
Not at all.
Also, consider that the different genetic subtypes are closely associated with particular risk groups—subtype M appears in MSM and IV drug users but not others, which doesn’t make any sense for a horizontally transmitted viral vector.
I’m not an epidemiologist (or a geneticist), but couldn’t that just be a founder effect perpetuated by MSM and IV drug users transmitting HIV much better amongst themselves than they transmit it to everyone else?
Most of the subtypes are linked to particular geographical regions in Africa, which points to a long history in humans (with M representing a novelty linked to novel behaviour).
I’m not seeing why this would be evidence for/against orthodox theories of HIV & AIDS. (And if I were being pedantic, again I’d suggest the relative insularity of MSM and injecting drug users as why subtype M’s linked with them, rather than the novelty of their behaviour as such.)
I’ll pass on commenting on your last three paragraphs, since what I know about retroviruses would fit on the back of a postage stamp. I will try checking Padian et al. again, though.
One of the more interesting hetero sero-discordant studies is the Padian 10 year study. Trying to isolate for hetero sexual transmission, they actually strictly eliminated all drug users by using actual drug tests—something that others have not done to my knowledge.
Yes, I don’t know any other studies that used direct drug tests. There is this Madrid study of heterosexual transmission that used indirect testing of “markers related to drug addiction (e.g., hepatitis C serology)” to check for drug use in addition to questionnaires, and its recorded transmission rate is quite high: 26%, out of 38 couples. However, it looks like a retrospective study.
We found only marginal significance for enrollment in the study prior to 1990 (OR = 1.9), not using condoms (OR = 1.7), and >300 unprotected penile-vaginal or penile-anal contacts (the median number of contacts) (OR = 1.6) [snip]
So large amounts of unprotected sex did not appear to be a very significant risk factor. The highest risk factor was just anal sex as a practice, not the number of contacts.
Although quantity of sex doesn’t seem to have made much difference, the unadjusted odds ratio associated with not using condoms bordered on statistical significance with a confidence interval of 0.95 to 3.01. After adjusting for the number of sexual contacts, that odds ratio went up to 2.1, becoming significant and equal to the adjusted odds ratio associated with anal sex. I notice too that after adjustment, STI history — a risk factor elsewhere associated with HIV transmission — was the risk factor with the highest odds ratio.
But what was really interesting in this group of some 600ish hetero non-drug users was that during the length of the study, there was not a single seroconversion, even though condom use in these couples was imperfect:
It would be more interesting if the relevant sample did contain 600 heterosexual non-drug users followed for the length of the study. However, the “no seroconversions” result comes from the study’s prospective part, which involved only “175 HIV-discordant couples over time, for a total of approximately 282 couple-years of follow-up [...] attrition was severe”. That’s a mean follow-up time of only 19 months per couple. Most couples probably got less follow-up time than that, because severe attrition would tend to negatively skew the follow-up time distribution, depressing the median.
That’s not all. The investigators didn’t just counsel the couples on safe sex, but also set up a 24-hour telephone support line, a newsletter and regular meet-ups. These measures were very effective in changing the couples’ behaviour: by the final follow-up, 15% of the 175 couples abstained from sex and 74% used condoms. So, at final follow-up, only 11% of the couples — nineteen in absolute terms — were at substantial risk of HIV transmission. The study’s statistical power to detect the small (in absolute terms) risk of heterosexual HIV transmission wouldn’t have been that great, especially given “the lack of incident STDs during the course of the study” (page 355).
There is zero evidence that non-drug using heterosexuals acquire the disease sexually, and studies such as this are evidence favoring a vertically transmitted virus.
You’re exaggerating. Even ignoring all other work on HIV’s epidemiology, there’s evidence of heterosexual HIV transmission in this very study! Its prospective aspect is just half of the research; there’s also the cross-sectional sample, which includes 230 couples recruited after the researchers began screening subjects for drug use in 1990. HIV transmission occurred in this subgroup, and after adjusting for estimated number of sex acts across the entire cross-sectional sample, there was no association between being enrolled before 1990 and HIV transmission (adjusted odds ratio = 1.0, 95% confidence interval = 0.98-1.0), so the transmissions in the cross-sectional group can’t just be attributed to the pre-1990 (i.e. unscreened) subgroup. (And again, recall the higher odds ratio for failing to use condoms and having a history of STIs. That sounds like more evidence of sexual transmission to me!)
Why does it only spread laterally into gay men and drug users, even though this is extraordinarily unlikely if it truly is horizontally transmitted?
But...it doesn’t only spread laterally into gay men and drug users?
I haven’t analyzed genital herpes and know very little about it, and regardless it is irrelevant. If the data says that HIV can not be sexually transmitted, and another disease has the same epidemologial data and is also called an STD, that somehow doesn’t magically change the data.
That’s true!
It just makes both classifications wrong.
Or your definition of an STI too restrictive.
There is no ‘luck’ and it all depends on the ratios. If only 1% of HIV+ people refuse treatment, but even just 10% of all “long-term non progressors” refuse treatment, then clearly treatment itself is part of the problem.
I think you have some implicit assumptions there to unpack.
It is strange and interesting that you think the cofactors only could work in favor of your privileged hypothesis. There is also the placebo effect to consider, and in a drug trial that is not double blind (as the AZT trials could not be) those who found out they were getting placebo believed they were going to die, and that encouraged wreckless behavior, not the other way around.
Do you have references for this?
Also, all the reports on LTNPs I have read are unanimous on lifestyle change being a distinguishing factor- reduction in drug use and bathouse type partying, general increase in healthier behavior.
Well, I expect that helps. (Which is not to say that switching to a healthy lifestyle halts the progression into AIDS.) I can’t imagine doing poppers and having casual sex is a good thing for anyone with HIV. (Come to think of it, isn’t it possible for someone who already has HIV to reinfect themselves with other substrains and make their infection worse?)
However, they still die at accelerated rates, and some eventually get AIDS.
Makes sense.
I think I’ll hold off on commenting on the last couple of paragraphs about AZT since (1) I really don’t know much about AZT, and (2) this discussion is becoming quite extensive and too much of a time sink for my liking.
Ok, so concerning the Padian study, I believe you have misread it, and I am to blame because I originally mislabeled it when I said:
One of the more interesting hetero sero-discordant studies is the Padian 10 year study.
I was wrong—it was not in fact a study of sero-discordant couples, and I apologize for that mistake, for it seems to have mislead you. This is evident in the abstract and is explicitly clarified elsewhere:
To examine rates of and risk factors for heterosexual transmission of human immunodeficiency virus (HIV), the authors conducted a prospective study of infected individuals and their heterosexual partners who have been recruited since 1985.
[...]
Briefly, couples were recruited without regard to the gender of the
index case or to the serostatus of the partner. [,,] Among couples where both were infected, the direction transmission was determined from detailed risk histories. [..] At the recruitment visit, the serostatus of the partner
was ascertained along with a risk history.
So they recruited non-drug using heteros of either sex who had steady partners, and some fraction of those partners were already infected—specifically 19% of the female partners and 2% of the male partners. They explicitly state there were no new infections in the abstract:
Over time, the authors observed increased condom use (p <0.001) and no new infections.
And again later:
However, given the retrospective nature of the cross-sectional aspect of our design (e.g., transmission occurred prior to entry in the study), past
We observed no seroconversions after entry into the study.
The last part happens to be in the ‘prospective results’ portion (where they switched focus to only serodiscordant couples), but should not be interpreted to somehow only apply to the post 1990 time period—as it says “after entry into the study”, and agrees with the “no new infections” in the abstract.
So I believe you have misinterpreted when you say:
However, the “no seroconversions” result comes from the study’s prospective part,
There was not a single new infection (seroconversion) during the entire ten years across all couples.
You are correct that they were counseled on condom use, but this does not seem to have influence actual reported condom use, even though the percentage of couples using condoms upon entry increased from around 50% to 75%, a significant fraction reported inconsistent usage:
Nevertheless, only 75 percent reported consistent condom use in the 6 months prior to their final follow-up visit. Forty-seven couples who remained in follow-up for 3 months to 6 years used condoms intermittently
So the key of this study and really all of the heterosexual transmission studies is that it is all just guess work. The 19% female and 2% male seropositive partners were just assumed to have acquired HIV sexually, but as this occurred prior to the study, the drug controls were not in place (and testing didn’t start until 1990). They are just assuming sexual transmission in these cases based on the strong unfounded assumption that HIV is sexually transmittable, they really have no idea.
What they did show, was that over about 4000 couple years, there was not a single new transmission in this drug-screened hetero sample. Using the 75% consistent condom use number, lets say then 1000 couple years of inconsistent usage, and perhaps then taking that to conservatively imply 80% condom usage on average for ‘intermittent’ users, you still have 200 couple years of unprotected sex, and not a single transmission. Remember that most of the partners (80%) are female, some practise anal, and that condom usage was reported as highest only for female index patients (male partners—paradoxically). Also, condoms are not at all 100% effective, even when used properly.
If there had been just a single seroconversion, that would correspond to a rate of transmission of 1 per 200 to 1000 years of sex, or perhaps a rate of 1 in 20,000 to 1 in 100,000 sex acts − 0.01 to 0.05%. But that single seroconversion did not happen. The actual transmission rate was exactly zero. As this study actually controlled for drug use cofactors it is the most accurate data I’ve seen for actual sexual transmission, and it shows that most studies grossly overestimate sexual transmission—the reality is there is no M->F transmission or it involves iv drug use.
The problem is simple—as untreated HIV presumably leads to death in 5-10 years, it needs to infect more than one person on average in that timespan just to maintain HIV population rate. To achieve a doubling in 10 years, it would need to infect 3 new people on average in that time.
To explain the growth rate in the early 80′s requires an absurdly faster doubling rate. This is not an STD. It is something else.
this discussion is becoming quite extensive and too much of a time sink for my liking.
Alright, I’ve had another look at Padian et al.’s paper. I did follow your lead in thinking the study was solely of sero-discordant couples, and I agree with you now that it actually wasn’t. However, the relevant part of the study is the prospective sample, which was solely of HIV-discordant couples, so my overall interpretation of the study’s nominally zero transmission rate remains unchanged.
They explicitly state there were no new infections in the abstract:
Over time, the authors observed increased condom use (p <0.001) and no new infections.
And again later:
[snip] We observed no seroconversions after entry into the study.
The last part happens to be in the ‘prospective results’ portion (where they switched focus to only serodiscordant couples), but should not be interpreted to somehow only apply to the post 1990 time period—as it says “after entry into the study”, and agrees with the “no new infections” in the abstract.
Right, but Padian et al. refer to the retrospective part of the study as the “cross-sectional” part (see page 351: “the retrospective nature of the cross-sectional aspect of our design”), implying there was no follow-up in that part. Without follow-up, they couldn’t have detected seroconversion after entry into the study, so the retrospective method wouldn’t pick up on post-entry transmissions however often they actually happened. So it’s a mistake to argue that no transmission happened in the retrospective group on the grounds that no transmission was observed, because the retrospective method can’t detect new transmissions.
So, although it’s technically true that the “no seroconversions” result applies to the whole period of the study, it would’ve been disingenuous for me to say so, because the researchers could only spot new seroconversions from 1990 onwards.
So I believe you have misinterpreted when you say:
However, the “no seroconversions” result comes from the study’s prospective part,
The study’s non-prospective part was incapable of detecting post-recruitment seroconversions, so the basis for the “no seroconversions” result is indeed the prospective part.
There was not a single new infection (seroconversion) during the entire ten years across all couples.
Well, there might’ve been new infections between 1985 & 1996 among the retrospective sample, but the study wouldn’t have detected those. The retrospective method would only detect those that happened in a couple before they entered the study.
You are correct that they were counseled on condom use, but this does not seem to have influence actual reported condom use, even though the percentage of couples using condoms upon entry increased from around 50% to 75%, a significant fraction reported inconsistent usage
The fact that a minority of the couples still didn’t use condoms consistently at their final follow-up doesn’t mean the counselling had no influence!
So the key of this study and really all of the heterosexual transmission studies is that it is all just guess work. The 19% female and 2% male seropositive partners were just assumed to have acquired HIV sexually, but as this occurred prior to the study, the drug controls were not in place
Only for the retrospective sample.
The calculations you do in the next couple of paragraphs seem to be based on both the retrospective & prospective subsamples, which exaggerates the number of couples in which new HIV transmissions could have been observed. New transmissions would only be observable among the couples in the prospective group.
So let’s run the numbers again for just that group. That group had 282 couple-years of follow-up, just 7% of your starting point of 4000 couple-years. Multiplying your final unprotected sex estimates by 0.07 gives me just 14 to 70 couple-years of unprotected sex.
Following on from that, how likely was a seroconversion for some hypothetical transmission rate? Let’s take 0.05%; 0.1% is unusually high for heterosexual couples, if I remember rightly, and 0.01% feels too low. Supposing the couples had 100 sex acts a year, we have (with a lot of simplifying assumptions) 1400 to 7000 sex acts. With 7000 acts at 0.05% a time, I get a 3% chance of no seroconversions. With 1400 acts, I get a 50% chance. This suggests that the likelihood of no seroconversions was not insignificant, so inferring a transmission rate of zero is likely to be a type II error. I also haven’t accounted for the 15% of prospective subgroup couples who became abstinent during the study.
As this study actually controlled for drug use cofactors it is the most accurate data I’ve seen for actual sexual transmission, and it shows that most studies grossly overestimate sexual transmission
Not with this lack of statistical power it doesn’t.
the reality is there is no M->F transmission or it involves iv drug use.
Whaaa?! Wouldn’t that imply that every female partner who became seropositive in the other studies got infected from secret lesbian sex or injecting drugs?
The problem is simple—as untreated HIV presumably leads to death in 5-10 years, it needs to infect more than one person on average in that timespan just to maintain HIV population rate. To achieve a doubling in 10 years, it would need to infect 3 new people on average in that time.
I don’t see that as a prohibitively high barrier. Especially because there’s not really just one transmission rate for each kind of sex act: transmission rate is moderated by other factors like stage of HIV infection, being infected with other STIs, and so forth.
To explain the growth rate in the early 80′s requires an absurdly faster doubling rate. This is not an STD. It is something else.
The early 80s growth rate wasn’t just driven by heterosexual sex.
Right, but Padian et al. refer to the retrospective part of the study as the “cross-sectional” part (see page 351: “the retrospective nature of the cross-sectional aspect of our design”), implying there was no follow-up in that part.
There was follow up starting in 1990. Basically they started the study by recruiting in 1985 and were originally focused on the retrospective aspect. Couples come in, fill out a questionairre and they attempt to screen out drug users and look for patterns in infected partners (couples where both are seropositive). Then in 1990, they began bringing couples in for examinations and follow up tests—“Physical examinations for both partners were initiated in 1990.” This is the beginning of the prospective part, but it doesn’t mean it is only valid for couples starting after that date, which comes from the very first sentence of the abstract:
To examine rates of and risk factors for heterosexual transmission of human immunodeficiency virus (HIV), the authors conducted a prospective study of infected individuals and their heterosexual partners who have been recruited since 1985.
The prospective part was not limited to only couples enrolling after 1990. That is only the beginning of the biannual checkups.
So, although it’s technically true that the “no seroconversions” result applies to the whole period of the study, it would’ve been disingenuous for me to say so, because the researchers could only spot new seroconversions from 1990 onwards.
Technically yes, but immediately in 1990 on the first follow-up they would have spotted any new seroconversions in any serodiscordant couples currently in the study. And they would have clearly mentioned any such detected seroconversions, and indeed they clearly mentioned that they detectected exactly zero.
But regardless, yes I did botch the total couple-years. The text implies that the 175 couple group with follow up was the total set of persistent couples:
Risk behavior at baseline and most recent (final) follow-up visit among 175 human immunodeficiency virus (HIV)-discordant couples recruited in Northern California from 1985 to 1996 (n = 175 couples with a total of 3,384 couple-months of follow-up)
Abstenence was between 0 and 14.5%, consistent condom use betwen 32% and 74%, and anal between 37 and 8%. We should probably also factor in that condoms are not 100% effective. Lets ignore that for a second and assume midpoints of the above numbers, with around 100 sex acts per year, or 10 per month. If ‘inconsistent’ means ~50%, I get ~2 unsafe acts per month, or ~6,000 unsafe acts. The majority of these couples (80%) are male seropositive, so the higher M->F numbers apply 0.1% to 0.5%.
The infection rate for P->V is supposedly 10 in 10,000, or 0.1% according to the CDC from the European study. The infection rate for P->A is supposedly 50 in 10,000, or 0.5%.
Sure it would have been better with 10,000 couples over many years, but how much specific negative evidence for sexual transmission does one require? Is there any specific positive evidence?
There is a larger set of data Deusberg points to for lack of sexual transmission, which is the hemophiliac population, around 75% of which tested positive for HIV in the 80′s. There were about 5,000 wives of HIV+ hemophiliacs, and the CDC reports 131 were diagnosed with miscellaneous AIDS diseases between 1985 and 1992. However, the particular diseases were age-related opportunistic infections, including 81% pneumonia—no KS, demantia, lymphoma, or wasting syndrome generally characteristic of typical AIDS. The 131 / 5000 appears to just be regular background rates for those illnesses. If AIDS was sexually transmitted, we should have seen evidence in this population of wives. Many of these couples were having sex for years before the blood was tested. This strongly contradicts any theories of a sexually transmitted etiological agent.
And if it is not sexually transmittable, then it is either only vertically transmittable or the entire theory is hopelessly flawed at a deeper level. I suspect the latter because the measured vertical transmission rates are not high enough to sustain plausible viral population.
the reality is there is no M->F transmission or it involves iv drug use.
Whaaa?! Wouldn’t that imply that every female partner who became seropositive in the other studies got infected from secret lesbian sex or injecting drugs?
Not at all—the data just shows that seropositivity is not sexually transmittable. A great deal of other evidence, combined with this clear lack of sexual transmission shows that seropositivity is clearly linked to risk groups with immunosuppression in general.
What you’re saying about Padian et al. just clicked for me. I’d got it into my head that they were allocating each recruited couple to either a retrospective track or a prospective track, with couples switching from the retrospective track to the prospective track after 1990, but without their data being carried over. But you’re saying the couples already enrolled in the study pre-1990 were automatically entered into the prospective part with their earlier questionnaires & lab work retained, right? That’d make more sense than how I first interpreted the paper. (Serves me right for skipping the abstract and diving straight into the methods section. Twice.)
Alright, let’s crunch some numbers.
Abstenence was between 0 and 14.5%, consistent condom use betwen 32% and 74%, and anal between 37 and 8%. We should probably also factor in that condoms are not 100% effective. Lets ignore that for a second and assume midpoints of the above numbers, with around 100 sex acts per year, or 10 per month.
Using the midpoints of the ranges is a good first guess in the absence of other information. However, I think there’s a good reason to use estimates much closer to the follow-up percentages (14.5%, 74% & 8%) than the baseline percentages (0%, 32% & 37%). The prospective results section says that “approximately 97 percent of behavior change was reported between baseline and the first follow-up visit”. That is, when couples started/stopped using condoms consistently (or abstaining, or having anal sex), they almost always did so before their first follow-up visit, suggesting the couples changed their behaviour shortly after counselling, not gradually. If so, then the baseline percentages only represent the couples’ behaviour distribution for a few weeks; after that, the distribution would be much better represented by the rates at final follow-up.
This could have a big impact on the surprisingness of the zero seroconversions result. Switching from the midpoint rates to the final follow-up rates boosts the abstinence rate to 14.5% and the consistent condom use rate to 74%, while cutting the “[a]ny anal intercourse” rate from 22.5% to 8%. So the neither-abstinent-nor-consistently-condom-using rate sinks from 39.7% to 11.5%. Carrying that forward, I get an unsafe act count ≈1600 instead of ≈5600 (assuming 50% condom use in that 11.5% of couples).
That of course makes a big difference: with a 0.1% risk per act (and I’d peg the risk as being far closer to 0.1% than 0.5%, given the low rate of couples admitting to any anal sex, let alone repeated anal sex), 1600 sex acts have a 20% chance of not causing any transmissions, but 5000 sex acts have only a 0.03% chance. Evidently the unlikeliness of getting no seroconversions under a hypothesis of low-but-nonzero transmission rates hinges on the numerical assumptions made about sexual behaviours. (And there are yet more tweaks one could make to the numbers: whether to adjust for the couples that were female HIV+ instead of male HIV+, how much to adjust for condom unreliability, how much to adjust for the time lag between HIV infection and showing up as HIV+ on a blood test, and so on.) A claim that HIV isn’t an STI is a hefty claim to hang on this single result.
Sure it would have been better with 10,000 couples over many years, but how much specific negative evidence for sexual transmission does one require?
If I’m remembering correctly, the only pieces of specific negative evidence I’ve seen cited here were the transmission rates’ small sizes (which I don’t see as evidence that HIV isn’t an STI, because the fact that a number is small doesn’t mean I can safely assume it’s nil), and the zero seroconversions result from Padian et al., the strength of which is arguable.
Is there any specific positive evidence?
I think the other studies of heterosexual transmission are at least suggestive. Explaining away the hundreds of female HIV seroconversions detected in those studies by assuming that each case of male-to-female transmission “involves iv drug use” does not seem credible to me. IV drug use is more common that it once was, but surely it’s not that common!
My scepticism is stronger still because a few of the studies have methodological features that would make transmission via needle sharing even less likely. I mentioned this Madrid study before. There’s also this ingenious study, which used sequence analysis on the subjects’ HIV samples to confirm that transmission was within pairs, making it less likely that non-index partners who seroconverted caught HIV from sharing needles with strangers.
Not at all—the data just shows that seropositivity is not sexually transmittable. A great deal of other evidence, combined with this clear lack of sexual transmission shows that seropositivity is clearly linked to risk groups with immunosuppression in general.
Immunosuppressed or not, a person won’t get infected by a virus unless that virus makes it into their body. Even with immunosuppression as a cofactor for HIV transmission, it can’t substitute for HIV transmission.
I almost forgot to ask for a reference for this:
There is a larger set of data Deusberg points to for lack of sexual transmission, which is the hemophiliac population, around 75% of which tested positive for HIV in the 80′s.
I’m unwilling to take Duesberg’s synopsis of these data on trust, and would want to see where he got his numbers from, and which methodological issues he might’ve glossed over. I can think of a few issues already, without even looking. The fact that the couples were having sex for years before getting tested in the 1980s wouldn’t mean much if HIV hadn’t been circulating in the blood supply for long. Different AIDS risk groups often have different constellations of AIDS-defining illness: Haitians often present with diarrhoea & TB, whereas US gay men often present with KS, for example, so I would guess haemophiliacs & their wives might have their own distinct AIDS-associated illnesses. Counting AIDS cases would underestimate HIV transmissions, because only some HIV+ wives would have progressed to AIDS. And so forth.
Also note this ‘ingenious’ study has an important point of evidence that does agree with the Padian study and points to a non-sexually transmitted etiology:
There was no significant difference in the rate of HIV transmission per coital act with inconsistent condom use, compared with no reported use, at any stage of infection.
The circumcision studies from Africa don’t tell us much either, as circumcision is associated with ethnic/cultural groups and thus drug use and other factors.
Immunosuppressed or not, a person won’t get infected by a virus unless that virus makes it into their body. Even with immunosuppression as a cofactor for HIV transmission, it can’t substitute for HIV transmission.
There are other more parsimonious explanations that don’t rely on a ‘virus’ at all, and HIV—as far as it exists as a rather arbitrary collection of DNA/RNA sequences, may not be a virus at all. It could just as easily be trash RNA being secreted in exosomes tagged for immune system garbage collection. It could be regulatory RNA exosome messages intended for other cells. It could be a mutant form of an endogenous regulatory RNA exosome. It could be an endogenous ‘virus’ that forms as a cancer-like mutation of normal endogenous regulatory RNA exosome communication. And yes, it could actually be a true exogenous RNA virus that just happens to be remarkably similar to sequences embedded in the human genome (such as the so called “HERV” sequences) - and just happens to look like typical RNA exosomes in the microscope.
But even if it is a true exogenous virus that can jump between cells and that is a huge if, there is astonishingly little evidence it causes much harm.
There is a mountain of evidence that drug use causes harm, and specifically that particular drugs linked especially to the gay community cause specific types of chronic accumulated immune damage.
Methanphetamine (speed) and its derivatives for example is tightly correlated with HIV/AIDS, it is endemic in the “party and play” gay community, and we have a large amount of evidence that Meth does significant long term harm.
Firstly, Meth is a hyper-stimulant of the “flight or fight” stress response. This stress response essentially temporarily shuts down the immune system and digestion to focus the body on a temporary threat. A lion may kill you in a matter of minutes, while your body’s normal symbiotes/parasites such as fungal candida are not going to do much in this time frame—so stress is bad for the immune system, but this is ok because stress normally is temporary.
What happens when go on a multi-day meth binge and hyper-stimulate your stress response? Well, we don’t entirely know, but it appears to be pretty bad for your immune system. And finally, the drug itself has potential DNA damaging effects through oxidative free radicals. This is a particular problem for any drugs that are often heated up and burnt in either the consumption or production phases, resulting in oxidative byproducts. The typical crack-cocaine ‘cooking’ procedure is especially bad in this respect.
The ‘immune system’ - which really should be called the ‘regulatory system’, is second only to the brain in complexity. It is responsible for not only protecting the body from foreign invaders, but also for general regulation of symbiotes/parasites in the gut, identification and control of rebellions (cancer), as well as normal tissue generation and regeneration (healing).
The CD4 cell pathway in particular is especially complex, and these cells are responsible for identification and long-term memory of particular antigens. They go through an extensive selection process to eliminate possible identification errors (auto-immune disorders). This system is especially sensitive to DNA damage, which is happening all the time—and these cells are expected to stick around for many years to hold antigen memory. They also use a random DNA shuffling process early on to generate their antigen recognition system, and these cells are bouncing around constantly in the blood in such a way that makes essential complex DNA repairs—double strand break repairs—much more difficult.
Consider the insults that AIDS patients are inflecting on this system: known potent stress inducing immuno-suppressants such as Meth and Cocaine type drugs, and oxidized byproducts of cooked drugs directly injected or smoked. Also consider that the rectum is second only to injection as a route into the bloodstream, and associated with anal sex are lubricants which can be absorbed. Has anybody seriously evaluated the long-term health effects of anal lubricants? I haven’t seen such a study. Consider that earlier in the AIDS era more toxic oil based lubricants, possibly containing benzoprene deriatives, were more common. Fortunately presumably safer water based lubricants are more common today, as the oil-lubricants can destroy condoms. All of this stuff goes—right up into the bloodstream.
And finally we should look at gay related intestinal disorders—as most of the CD4 cells are actually in the gut, and gut problems are endemic in gay men. Whether it’s semen absorption, lubricants, or anal douching is unclear, but it appears to cause some chronic gut problem—and possibly leaky gut syndrome, allowing more foreign antigens to pass directly into the blood. Exposure to all these strange antigens may simply confuse the immune system. Now combine that with chronic meth use and you have a clear recipe for AIDS which doesn’t require a virus. Overall, the gut/immune system is designed for forward entry.
The hetero groups that get AIDS in the west tend to be hardcore drug users. The other known group is hemophiliacs. The “AIDS” each of these groups gets are quite different and really only have the low CD4 count and blood reaction test in common—which really are just general markers of a dysfunctional immune system. Hemophilliacs have a genetic disorder of the blood and never lived long until the AIDS era anyway, and injecting foreign protein for the clotting agent is immuno-suppressive in itself.
AIDS, like cancer, is something that anybody can get—but most will not progress to AIDS or cancer until they are already quite old, and will usually die of something else well before that. AIDS is really just a common immune disorder—the elderly often have it to some degree—lower CD4 counts and opportunistic infections. You can accelerate the aging of your immune system and progress to AIDS faster by chronic use of immune supressing hyper-stressors such as Meth/coke drugs and or direct toxic DNA damage through injecting or absorbing (anally) foreign matter into the blood.
None of this causes much immediate damage, but like smoking it ages particular vulnerable systems, probably through accumulated DNA damage, and this is why many people who quit eventually will progress to AIDS anyway a decade later or so—the damage has already been done, just as many smokers who quit will still progress to lung cancer at an accelerated rate.
But the insults that these risk groups are doing to their blood and lymph are considerably worse than smoking. Although notice there is a huge amount of overlap—someone who chronically smokes crack cocaine is much more likely to die of some lung infection than say karposi’s sarcoma.
Also note this ‘ingenious’ study has an important point of evidence that does agree with the Padian study and points to a non-sexually transmitted etiology:
There was no significant difference in the rate of HIV transmission per coital act with inconsistent condom use, compared with no reported use, at any stage of infection.
Flicking to page 354 of Padian et al. I see this: “the practice of anal sex and lack of condom use have remained strong predictors of transmission since the beginning of the study”. And table 2 of the paper suggests that not using condoms is a statistically significant transmission risk factor, after adjusting for number of contacts (as I previously mentioned). I would not interpret that as agreement with a finding of “no significant difference”.
The circumcision studies from Africa don’t tell us much either, as circumcision is associated with ethnic/cultural groups and thus drug use and other factors.
This argument might go through for observational studies, although even there I’d want a quantitative argument for why I should expect those confounders to have as strong (or stronger) an effect as circumcision’s apparent effect. But I also referred to three large randomized trials, and randomization reduces the association between confounders and treatment effects to statistical noise — that’s why people conduct randomized trials. So I still regard the trials as strong evidence for circumcision having an effect on HIV transmission; confounders don’t have a substantial effect on the results of randomized trials unless the randomization process was faulty.
(Incidentally, my original links to the 2nd & 3rd trials are now broken. Hereare alternative links, although they may be paywalled.)
I’m skipping over the paragraphs on whether or not HIV is a virus since what HIV is specifically doesn’t bear on the point I was trying to make, which is that cofactors can’t subtitute for exposure to HIV (whatever one thinks HIV is).
There is a mountain of evidence that drug use causes harm,
Agreed.
and specifically that particular drugs linked especially to the gay community cause specific types of chronic accumulated immune damage.
Even if I grant you that, it doesn’t mean much to me unless one of those “specific types” of immune damage is the massive reduction in CD4 cell counts characteristic of AIDS. There are different kinds of immunosuppression, and it won’t do to presume that because something causes one kind of immunosuppression, it causes the kind of immunosuppression associated with AIDS.
At any rate, I suspect properly accounting for HIV+ status eliminates the link between whichever drugs you have in mind and AIDS. (Note that I am not denying any association between drug use and some form of immunosuppression — just non-spurious associations between drug use and substantial depletion of CD4 counts.) This 1993 Nature report describes results from the Multicenter AIDS Cohort Study. Check out the graph: there is a clear difference in CD4 count between seronegatives & seropositives, and only the seropositives suffer a downward slide in CD4 counts over the years, whereas differing levels of drug use show only meagre effects on CD4 count trajectories.
Methanphetamine (speed) and its derivatives for example is tightly correlated with HIV/AIDS, it is endemic in the “party and play” gay community, and we have a large amount of evidence that Meth does significant long term harm.
But how much does it affect CD4 counts?
What happens when go on a multi-day meth binge and hyper-stimulate your stress response? Well, we don’t entirely know, but it appears to be pretty bad for your immune system. And finally, the drug itself has potential DNA damaging effects through oxidative free radicals. This is a particular problem for any drugs that are often heated up and burnt in either the consumption or production phases, resulting in oxidative byproducts.
But how much do they affect CD4 counts?
Skipping the background commentary on the immune system and the speculation about lubricants & intestinal disorders.
The hetero groups that get AIDS in the west tend to be hardcore drug users. The other known group is hemophiliacs. The “AIDS” each of these groups gets are quite different and really only have the low CD4 count and blood reaction test in common -
CD4 counts below 200-400 are AIDS’ key feature. The Nature paper I linked refers to “CD4+ T-lymphocyte depletion” as “the primary pathognomonic feature of AIDS”. Opportunistic infections of course vary in prevalence across subpopulations, but that doesn’t somehow negate the common symptom that allows them to get a foothold: low CD4 counts.
which really are just general markers of a dysfunctional immune system.
Do you have references for this?
Hemophilliacs have a genetic disorder of the blood and never lived long until the AIDS era anyway, and injecting foreign protein for the clotting agent is immuno-suppressive in itself.
But how much does it affect CD4 counts?
AIDS, like cancer, is something that anybody can get -
If they have HIV. Or idiopathic CD4+ T-lymphoctyopenia, come to think of it. Other than that...?
but most will not progress to AIDS or cancer until they are already quite old, and will usually die of something else well before that. AIDS is really just a common immune disorder—the elderly often have it to some degree—lower CD4 counts and opportunistic infections.
Hedging with the phrase “to some degree” makes that statement too vague for me to get a handle on, and it’d help to put a number on it. At any rate, CD4 counts don’t appear to be much lower among the elderly than among younger adults. A quick poke around for CD4 reference counts brings up this Mayo Medical Laboratories page, which gives a range of 424-1509 for people aged 18-55, and a range of 430-1513 for people aged 55+.
You can probably anticipate what I’d say/ask for the rest of the parent post, so I’ll save you the repetition.
This thread is now at 4.5*10^4 words (counted by copying into a text editor, and find/replacing to delete words that’re actually headers or vote/navigation links). I believe it should have been taken off-line at approximately the 5*10^3 word mark, if not sooner.
I admit I’m obsessively addicted. The more I look into it, the more I have found that HIV science has gone horribly, horribly wrong, and ‘HIV’ - whatever it is—if it even exists—is neither necessary nor sufficient to cause AIDS.
Considering that we have spent hundreds of billions of dollars on this hypothesis, this has larger implications for rationality and the scientific establishment in general.
Even if I grant you that, it doesn’t mean much to me unless one of those “specific types” of immune damage is the massive reduction in CD4 cell counts characteristic of AIDS. There are different kinds of immunosuppression, and it won’t do to presume that because something causes one kind of immunosuppression, it causes the kind of immunosuppression associated with AIDS.
This is absolutely true, and is a very good point. However, keep in mind that seropositivity is not a direct measure of HIV, and isn’t even especially correlated with HIV (see my reply in the other thread). Seropositivity is a rather good measure of CD4 cell decline—simply glance at that graph in the Nature paper and you can see that. Although I should point out I’m not sure if it’s actual cell loss that is measured or simply more CD8 expressing T-cells vs CD4.
Also note that there was no body of non-users of nitrates in the homo risk group in this study—they were split simply into ‘light’ and ‘heavy’, and the heavy users were twice as likely to get KS—I’d say that is a rather significant correlation.
This study has some flaws for looking at toxological causes though, as it was only looking at rather recent drug use (24 months), which is not quite the same as use history overall.
But how much does it affect CD4 counts?
I’m not sure about Meth’s effects on CD4 counts in particular, but heavy cocaine use has a strong depleting effect on CD4 counts. First google result
But there are other factors in the homosexual risk group, the most important of which is simply semen. Semen is loaded with immunosuppressants that are designed to temporarily and locally deactivate the female immune system in the vaginal tract. One of those components are the prostglandins. It appears that evolution has struck a balance between semen’s need to disable immunity and the female’s need to regulate opportunistic microbes in the vagina (namely candida) - this balance sometimes fails and yeast infections result.
AIDS is in general associated with candidiasis—yeast infections—which overgrows in the rectal tract and eventually in the blood, and some of the seminal components absorb into the blood. Large-scale overuse of antibiotics to combat STD’s in the gay community is another significant cofactor, but semen itself may be a major part of the problem.
Many papers about semen’s immune suppression effects are a simple google search away—here is one typical example.
They found that just seven daily rectal semen insertions had a marked immune suppression effect, but only in male rats, female rats didn’t seem to be particularly effected.
You seem to think that the CD4 count decline is somehow completely explained by HIV theory. It is not. The CD4 count decline is the defining feature of AIDS, but HIV’s role, if any, is theoretical and not well understood. So it makes sense to look at all the factors involved—for there are many independent immune suppressing factors in the primary AIDs risk groups—homosexuals and injection drug users.
In the original AIDS defining population of homosexuals, AIDS is associated with a tightly bundled set of cofactors:
passive anal sex
drug use
a history of a large number of past sexual partners and STD’s
a history of heavy antibiotic treatment
More on all the known immune suppressing factors in the gay cohort here. All of this needs to be taken into consideration before one starts chasing some new ‘virus’.
The drugs have changed over time (meth and MDMA being more popular now), but the correlation has remained.
The second significant risk group of AIDS patients appears to be injection drug users—really crack cocaine injectors in particular, and cocaine is known to deplete CD4 cells and cause AIDS all by itself.
Hemophilliacs have a genetic disorder of the blood and never lived long until the AIDS era anyway, and injecting foreign protein for the clotting agent is immuno-suppressive in itself.
But how much does it affect CD4 counts?
I don’t know. Do you know? Do you want to investigate this? How? Keep in mind that before the AIDS era, hemophiliacs didn’t live all that long. We simply didn’t have much data on their longer term health problems. Then in 1985 the HIV panic mania spread, and the hemophiliac population was tested with Gallo’s “HIV’ test—which really is just a CD4 decline surrogate test. And we found that a big % of this population had declining CD4 counts and somewhat AIDS-like blood. What does this really mean?
And their wives don’t get it, btw. Neither do non-drug using prostitutes. Porn actresses in general do not appear to be at an elevated risk of developing AIDS either. None of this makes any sense for a sexually transmittable viral theory, but it makes perfect sense if AIDS is caused by primarily toxological chronic immune suppression.
At any rate, CD4 counts don’t appear to be much lower among the elderly than among younger adults.
I’m not so sure about that. I’m not sure that low CD4 counts in particular is common in the elderly, but compromised immune function is a typical problem of the elderly:
“Opportunistic infections occur with greater frequency or severity in patients with impaired host defenses. Growing numbers of HIV-infected persons, transplant recipients, and elderly persons are at increased risk.”
“Elderly persons have defects in T-cell immunity that result in increased incidence and death from TB”
You can probably anticipate what I’d say/ask for the rest of the parent post, so I’ll save you the repetition.
I won’t reply to this comment in full, but there’s a little loose end of my own making here, and I should tie it up:
You can probably anticipate what I’d say/ask for the rest of the parent post, so I’ll save you the repetition.
?
“But how much does it affect CD4 counts?” (In response to the references to meth, cocaine, direct DNA damage due to injection and rectal absorption of foreign matter, and smoking.)
Evidently the unlikeliness of getting no seroconversions under a hypothesis of low-but-nonzero transmission rates hinges on the numerical assumptions made about sexual behaviors.
A claim that HIV isn’t an STI is a hefty claim to hang on this single result.
Strong claims shouldn’t hinge on a single study, but this study can be used to update probabilities for certain theories. You can think of it as eliminating possibilities.
Namely it eliminates or vastly reduces any hypotheses involving a typical STD transmission route. It allows for a very small possible horizontal transmission rate, but the most likely cluster is centered around zero. That doesn’t prove it is zero, it is just that this evidence strongly favors zero transmission rate theories over all others.
Is there any specific positive evidence?
I think the other studies of heterosexual transmission are at least suggestive. Explaining away the hundreds of female HIV seroconversions detected in those studies
The what? I don’t think there is a single “female HIV seroconversion” to be “explained away” in any of those studies. From what I understand, and what Padian et al claim, the Padian study is the only properly controlled prospective study of heterosexual transmission. The other studies are just observational guesswork that are all circularly dependent on the notion that seropositivity is transmissible—they see a couple where both test positive and they just assume it was sexually transmissible—hardly anything resembling evidence for the theory—just circular logic.
by assuming that each case of male-to-female transmission “involves iv drug use” does not seem credible to me. IV drug use is more common that it once was, but surely it’s not that common!
First of all, in the other theories, there is no transmission to explain—and it certainly doesn’t have to involve iv drug use.
You have to understand what exactly seropositivity actually means. It is a blood test that was specifically designed to classify “aids-like” blood. Gallo developed it by comparing and testing a large amount of antibody combinations (biological IDs essentially), until he found a combination which successfully partitioned the AIDS-like and pre-AIDS-like blood from the normal blood. There are a host of other conditions that can cause full or partial seropositivity—think of it as a semi-general measure of CD4 immune malfunction. And actually, ‘malfunction’ is not even the right term, as one can test positive under some normal circumstances as well—such as pregnancy or during the course of some illnesses.
Testing positive multiple times, for no other apparent reasons, is a clear sign of some persistent CD4 immune malfunction which is highly correlated with full-blown AIDS in the future.
I glanced at the Madrid study and find it largely worthless compared to the Padin study. It is small, not properly controlled, and not prospective. They found higher “viral load” in couples that were both positive vs couples where only one partner was positive? That makes sense simply because as viral load loosely correlates with degree of sickness, we expect that to be correlated in couples. More sick people are more likely to not have partners at all or have sick partners.
You would see the exact same effect in smokers, and keep that analogy in mind when looking at any of this data.
Your “ingenious study” is not well controlled for drug use, and in fact barely even mentions it. As HIV/AIDS is highly correlated with drug use in all the epidemological data I have seen in the west, I don’t think this study allows us to differentiate much of anything.
For example, if you want to determine if lung cancer is predominantly caused by a sexually transmittable virus or toxicological effects of smoking, you need to design studies that carefully differentiate between the two. If you don’t screen for drug use (or smoking) you won’t learn much. Smoking (and drug use) are both highly correlated in long-term couples. If you just simply assume from the get go that the sexually transmitted viral theory is correct, you would naturally see an apparent low rate of transmission proportional to the length of time the couple is together (because this correlates with the smoking behavior ‘catching’.)
So to show that lung cancer is caused by a sexually transmitted vector, you would need to focus on non-smokers. That is why the Padian study is useful, and this African study you point to is not useful.
The part that you seem to think is ingenious—the so called “sequence analysis”, I do not find necessarily ingenious or able to “confirm that transmission was within pairs” in the slightest.
If you want to get into the side discussion on “viral load” and viral DNA comparison based on PCR techniques, it’s critical that you understand Kary Mullis’s objection. Kary Mullis won the nobel for inventing PCR, and he is a strong critic of the whole HIV theory, and the entire interpretation of genetic data based on the technique he invented.
Basically, PCR-like techniques allow you to detect DNA sequences that match a partial fragment, and they allow you to massively amplify those matches—allowing one to find a needle in a haystack by duplicating the needle into a new haystack, so to speak. It’s more useful for qualitative vs quantitative results. The problem with the whole idea of using PCR to test for “HIV DNA” is multi-fold. First, HIV-DNA is allowed to be any of a vast set of sequences—presumably because of it’s massive “mutation” potential. The human body is floating in a sea of RNA and DNA sequences, most of which we know little about—large amounts of various types of RNA that is used to control gene expression, regulatory computation, and regulatory signaling between cells.
So out of that sea of DNA/RNA you get in a tube, a huge set of 10bp-ish sequences are rather arbitrarily determined to be “HIV”, and then one tests many partial sequences and usually finds some similar-ish matches. If you use this PCR test on anybody you will always get some positive results—everybody has some amount of “HIV-ish” genetic material circulating in their blood normally. Comparing sequences in this way is fraught with methodological problems—if you pick some random sequence you will probably find something similar in someone else’s blood, so there is a huge amount of potential sample bias—somewhat like looking for pictures of crystals in ice patterns or looking for coded messages in the bible. There is so many random sequences that it is easy to find some that match, focus on those, and then ignore all the non-matches. A real true similarity comparison would involve a tremendous amount of sequencing on a scale that is—as far as I can tell—never done or not even feasible today. It is not as if PCR gives us some complete snapshot pictureof all the DNA/RNA floating around.
And finally, keep in mind that any way you slice it—we should expect to see sequence similarities in these couples, as they are genetically related—from the same area in africa and much more related on average than two random samples of homo sapiens.
Strong claims shouldn’t hinge on a single study, but this study can be used to update probabilities for certain theories. You can think of it as eliminating possibilities.
That’s my issue — I don’t think Padian et al.’s zero seroconversions result is sufficiently strong to outright eliminate a possibility, unless one’s already assigned a low prior to that possibility. Personally, I walked into this discussion with a very high prior (something like 99%) for HIV being sexually transmissible to some nontrivial (more than, say, once in every million unsafe sex acts) extent, and the Padian et al. result is not a strong one, so my prior is essentially unchanged.
Namely it eliminates or vastly reduces any hypotheses involving a typical STD transmission route. It allows for a very small possible horizontal transmission rate, but the most likely cluster is centered around zero.
Since the prior estimates for sexual transmission I’ve seen are already very small (on the order of 0.01% to 0.1%), the Padian et al. result doesn’t really clash with them that much. I also doubt “the most likely cluster” is centred on zero if one accounts for all of the evidence in the study, rather than focusing exclusively on the zero seroconversions result.
That doesn’t prove it is zero, it is just that this evidence strongly favors zero transmission rate theories over all others.
It favours a zero transmission rate strongly only if one makes particular strong assumptions about the sexual behaviour of the study’s subjects, and disregards the evidence of risk factors.
The what? I don’t think there is a single “female HIV seroconversion” to be “explained away” in any of those studies.
Let’s return to one of the papers that kicked off this discussion, as it has a few examples. From page 810: “seroconversions occurred in three male and seven female contacts after enrolment in the study” (that’s not even counting whatever seroconversions had to have occurred in those subjects already HIV+ at the start of the study). There must be some explanation for those seven seroconversions.
From what I understand, and what Padian et al claim, the Padian study is the only properly controlled prospective study of heterosexual transmission. The other studies are just observational guesswork that are all circularly dependent on the notion that seropositivity is transmissible—they see a couple where both test positive and they just assume it was sexually transmissible—hardly anything resembling evidence for the theory—just circular logic.
Whether or not one believes HIV is sexually transmitted, seroconversions occurred. What were their causes, if not HIV infection due to sexual transmission?
First of all, in the other theories, there is no transmission to explain—and it certainly doesn’t have to involve iv drug use.
Where does the HIV come from if not an external source?
I glanced at the Madrid study and find it largely worthless compared to the Padin study. It is small, not properly controlled, and not prospective.
I do not see the Madrid study as “largely worthless”, though I’d give it less weight than the Padian et al. study for the reasons you give. (I should emphasize that I’m talking about the Padian et al. study as a whole there; I maintain my reservations about the zero seroconversions result.) Still, the Madrid study sample’s not particularly small compared to the number of Padian et al. couples who consistently had unprotected sex and were followed up prospectively.
Your “ingenious study” is not well controlled for drug use, and in fact barely even mentions it.
Yes. The point I was making was that with the sequence analysis confirming the source of the transmission, the probability of any given seroconverter having been infected by IV drug use with strangers is less than if the researchers hadn’t done the sequence analysis (although of course still more than zero). So, to have me agree that the HIV infections are due to IV drug use, I would have to be convinced that the seroconverters had been sharing needles with their partners. And...
As HIV/AIDS is highly correlated with drug use in all the epidemological data I have seen in the west,
...as the study took place in Uganda, I find it very unlikely that even half of the seroconverters were infected by sharing needles (especially since none of the subjects reported injection drug use). Unless you are now arguing that seroconversion doesn’t actually indicate HIV infection (and I can’t tell whether you are or not), I expect you can see why I’d want alternative explanations for each of these seroconversions.
So to show that lung cancer is caused by a sexually transmitted vector, you would need to focus on non-smokers. That is why the Padian study is useful, and this African study you point to is not useful.
The African study, I’d say, is weaker evidence than the Padian study. At the same time, I think it’s absurd to write it off as “not useful”. At the risk of repeating myself, my reasoning goes like this: some number of subjects acquired HIV during the Ugandan study; exposure to HIV is necessary for infection; it is not credible to suppose that every HIV exposure that led to seroconversion is attributable to IV drug use. If there were only four or five seroconversions, I’d say it was statistically possible. In fact, the study reports that out of 239 monogamous couples that were initially HIV-discordant, 72 “acquired HIV during follow-up”. The probability that all 72 of these Ugandans acquired HIV by IV drug use is surely astronomically small.
If you want to get into the side discussion on “viral load” and viral DNA comparison based on PCR techniques,
Not especially, to be honest.
it’s critical that you understand Kary Mullis’s objection. Kary Mullis won the nobel for inventing PCR, and he is a strong critic of the whole HIV theory, and the entire interpretation of genetic data based on the technique he invented.
I’m not much impressed by Mullis’s Nobel credentials. There are quiteafewNobelists who got the prize and promptly started dabbling in crankery. (Including, as it happens, Luc Montagnier, so this isn’t just an issue for people who downplay the links between HIV & AIDS.) Jim Watson co-discovered DNA’s structure, but I’m not about to take all his proclamations about genetics at face value.
Anyway, I haven’t seen anything in the Uganda study report to suggest they used PCR in so sloppy a way as you’re suggesting, and I doubt they’d have much to report if they had. As such, it’s hard for me to avoid the feeling that your remarks about PCR are something of a fully general counterargument against HIV sequencing.
And finally, keep in mind that any way you slice it—we should expect to see sequence similarities in these couples, as they are genetically related—from the same area in africa and much more related on average than two random samples of homo sapiens.
Right, but two samples of virus from a couple where one member infected the other will nonetheless be far more genetically similar on average than two samples of virus from randomly selected infected people in Rakai.
Whether or not one believes HIV is sexually transmitted, seroconversions occurred. What were their causes, if not HIV infection due to sexual transmission?
First of all, in the other theories, there is no transmission to explain—and it certainly doesn’t have to involve iv drug use.
Where does the HIV come from if not an external source?
I’m having difficulty squaring some of your comments on seropositivity and HIV testing with the high reported sensitivity & specificity of properly conducted HIV tests.
First off, before we get into anything else, we need to understand and agree on what seropositivity actually means. Seropositivity means a positive result on an antibody test such as western blot, to some combination of antigens identified by Gallo in 1985 in his large scale blood screening tests. He did a large number of tests on transformed (immortalized) cell lines derived from AIDS patients and found a combination of antigens that could screen blood—separating AIDS and pre-AIDS blood from regular blood.
The problem is he (like Motagnier) failed to isolate the ‘virus’, and most or all of the antibodies in the test react or cross-react with antigens to opportunistic microbes (candida namely) and cellular debris. The p24 protein in particular is essentially just a normal cellular wall or microvescile component—so the ‘HIV’ test is really just a general test of opportunistic infection and apoptosis or immune directed killing of CD4 cells (possibly due to widespread viral parasite burden). It is not a measure of ‘HIV’, it is a direct measure of declining CD4 cells and AIDS or pre-AIDS.
The antibody tests are not standardized geographically or temporarily, so it also makes it very difficult to compare across studies—“seropositivity” means different things in different places and times.
As just one random example—most dogs typically have a mix of ‘HIV’ antigens, and are HIV ‘seropositive’ in whole or in part:
reported that 72⁄144 (50%) of dog blood samples “obtained from the Veterinary Medical Teaching Hospital, University of California, Davis” tested in commercial Western blot assays, “reacted with one or more HIV recombinant proteins [gp120--21.5%, gp41--23%, p31--22%, p24-- 43%]”
You post a link to a paper which supposedly shows the ” high reported sensitivity & specificity” of HIV tests. This is not actually what that paper is about, but it references several other papers for this claim—the first I investigated being this. The important quote:
Thirty-fourwomentested HIV-1 positive
with both rapid test and EIA, and all
were confirmed by Western blot
(prevalence=7/1000).
So they are just using Western blot as ‘confirmation’. So they are just using one antibody test to confirm another antibody test—which of course is rather ridiculous.
To actually compute the sensitivity and specificity for a “HIV” test, one needs a gold standard such as viral isolation or perhaps a DNA test. Unfortunately HIV can not be isolated, either because it doesn’t exit or it exists in only minute quantities.
But one can attempt to use the presumed viral DNA as a gold standard, and the result is extremely poor sensitivity and specificity:
Poor sensitivity is perhaps a gross understatement—the study actually shows that around 18-25% of the population at large test positive for ‘HIV DNA’, and this is only weakly correlated with seropositivity.
You completely dismiss Mullis’s argument based solely on an ad hominem “not much impressed by Mullis’s nobel credentials” without seeming to acknowledge or understand the argument itself.
Seroconversion in the west is closely correlated with AIDS or pre-AIDS. This does not appear to be as true in Africa, so we are generally talking about two different worlds. Part of this may be genetic (black americans have amazingly higher seropositvity in general), the other part may relate simply to higher precedence of opportunistic infections and antigens that seropositivity measures. KS for example is vary rare in the west and along with systemic candidaisis was part of the original AIDS definition, but it is one of the most common cancers in Africa.
Unless you are now arguing that seroconversion doesn’t actually indicate HIV infection (and I can’t tell whether you are or not),
I am arguing that.
Seropositivity does not strongly correlate with ‘HIV’ infection (by DNA test), which is why it is better to discuss AIDS itself as being sexually transmittable or not.
The Gallo blood test is tightly correlated with AIDS (at least in the west) - simply because that is what it was designed to do, so you can use that as data for AIDS transmission discussions.
Unless you are now arguing that seroconversion doesn’t actually indicate HIV infection (and I can’t tell whether you are or not),
I am arguing that.
OK. At this point, I’m going to have to disengage and walk away from this debate. I’m realizing that the inferential distance between us is far bigger than I originally thought, and trying to bridge it would need me to considerably ramp up the effort I’m already putting into this. (Even then I can imagine this going on indefinitely, which isn’t a very appealing prospect to me, nor to other Less Wrong posters, by the looks of it.)
I’d still like to respond briefly to one part of your comment, which comments on my own words rather than HIV/AIDS:
You completely dismiss Mullis’s argument based solely on an ad hominem “not much impressed by Mullis’s nobel credentials” without seeming to acknowledge or understand the argument itself.
It’s wholly legitimate for me to respond to someone citing Mullis’s credentials (as if I didn’t know about them already) by explaining why I give them little weight, and my next paragraph was meant to summarize why I gave “your remarks about PCR” (that is, those you paraphrased from Mullis) short shrift. In other words, I acknowledged the argument by rejecting it.
I’m glad you can walk away, I have a harder time initiating that. I’m curious though about the direction of the inferential distance you see—do you have a biology background?
The dissidents point to a rather surprising pile of evidence that the serological HIV tests are based on rather general, cross-reactive antibodies, and this is essentially a fundamental flaw in HIV science which has never been corrected. Now it may be that the orthodoxy has a really good counter to this, but if they do I have yet to find it. The orthodox position on this, from papers linked to wikipedia, points to studies which measure the sensitivity of various HIV antibody tests by comparing them to . . other HIV antibody tests.
The few large double-blind meta-studies that compare the different antibody tests to PCR tests show terrible sensitivity and specificity between the two, and I haven’t seen the orthodox counter to this. So something is wrong with the antibody tests, the PCR tests, or the whole thing. I imagine it’s a little bit of both—the antibody tests are cross-reactive (hence many dogs test positive), and PCR tests are difficult and subject to experimenter bias.
Perhaps the orthodox counter is that there are a whole big host of HIV related viruses, and the antibody tests are cross-reactive across these related species. This seems to then just beg more questions than it answers, and doesn’t circumvent some of the specific non-viral cross-reactions the dissidents point to.
My paraphrase of Mullis’s argument may actually be a mix of other dissident positions. I just rechecked that part of his book and he covers the difficulty of PCR and the confirmation bias but largely in regards to the OJ trial. On HIV he mainly rehashes Deusberg’s argument.
I’m curious though about the direction of the inferential distance you see—do you have a biology background?
None at all. (I expect the inferential distance would be even greater if I did. If I had personal experience of working with retroviruses, for instance, I reckon my prior probabilities for claims like “HIV can not be isolated” or “HIV doesn’t exist” would be far, far less than they are. And they are already very low.)
To actually compute the sensitivity and specificity for a “HIV” test, one needs a gold standard such as viral isolation or perhaps a DNA test. Unfortunately HIV can not be isolated, either because it doesn’t exit or it exists in only minute quantities.
When ‘HIV’ was first ‘discovered’ in the original papers by Gallo and Montagnier, they had difficulty isolating and didn’t publish pictures from what I understand—that didn’t happen until years later. Gallo’s great discovery for HTLVIII was based on running a lager number of antigen/antibody tests with an immortalized cell line to find an antibody test that could screen AIDS and pre-AIDS blood from regular blood. That is the basis of all the current HIV tests.
The first published pictures came more than a decade later, and they showed that “HIV isolate” really consists largely of cellular debris and microvesciles. In these EM photos, they do find some occasional particles of roughly the right size and label them as “HIV”, but they could also just be any of a number of other things, and for all intents and purposes, HIV ‘particles’ look like regular microvesciles.
The titles of the papers say it all:
“Cell membrane vesicles are a major contaminant of gradient-enriched human immunodeficiency virus type-1 preparations”
“Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations”
I have lost the link, but there are better more recent pictures taken with ATM, and they show that for all intents and purposes, it’s impossible to distinguish ‘HIV’ from regular microvesicles that bud from the cell wall naturally. If HIV can be said to exist at all as a unique exogenous virus, it is only because of unique RNA content in the microvesicle, and in this sense is very much unlike all other known viruses.
Of course, the part of HIV’s genome which is supposed to code for the outer envelope is pretty much the same as the endogenous sequences that already exist in the human genome—the HERVs.
I would have given more creedence to this view at the beginning of this whole inquiry, but in another branch several other posters found some large meta-analysis studies, and low and behold they confirm and agree with the old CDC European study. I discuss that here
Of note is that the infection rate in 1st world countires agrees with the original CDC European Study, and the infection rate in Africa/3rd world appears to be 3-6 times higher. Metastudies which mix 1st and 3rd world results get rates somewhere in between.
Some of these metastudies were of thousands of individual studies, and say what we will about them, I think they nail down the real world transmission rates, and the 1st world rates are just as low as I originally quoted (or lower)
Effects like this surely can increase transmission rates in specific instances, but for epidemilogical modelling we are interested in the average rates—and note as I analyzed elsewhere, the original CDC European study does attempt to control for condom use—it intends to show infection rates for unprotected sex. I don’t think you can so easily dismiss all these studies and the work that has gone into computing these transmission rates.
This is certainly a possibility and fits what we know with viruses—variable genetic resistance is to be expected.
However, what is important is how one samples and when. If you take a sampling of survivors years later, then sure you can expect to be finding survivors due to genetic resistance.
But if you sample a subset based only on the criteria that they refuse medication after testing seropositive, then that is a very different sampling, and you should expect it to be largely uncorrelated from genetic resistance (unless you want to argue that people with genetic resistance are strongly expected to resist medication!, but I hope you won’t take that route)
You do bring up a potentially valid criticism:
Possibly, but I don’t find a reason why we should expect this without specific evidence—from what I understand the HIV-1 virus variants spread diffusely in specific at-risk subgroups. It would help the case if the study had more widely distributed patients, and maybe there are other such studies, but it isn’t strong evidence against. We can’t expect many patients to have resisted medicating, and those that did would tend to be clustered geographically in regions where some cluster of doctors were allowed to hold that view and resist medication for a long period of time and study the patients. From what I understand, this was not allowed to happen in the states.
You raise some further methodological questions:
I don’t know, and yes these are interesting questions, and it would be useful if there was a meta-study of all long-term survivors/non-progressors.
Yes, this would be interesting, but note that we shouldn’t expect these people to have full life expectancy, in either theory—as seropositive status is clearly a marker for ill-health. The bigger question is does refusing medication increase lifespan? That is the central point.
Even if they all died after 12 years on average, that still may be better than typical, for example.
A follow up would be interesting, but lack thereof isn’t necessarily a red-flag. They are going to die at some point, and probably much earlier than seronegatives. The question is one of statistics.
As to your questioning of whether these are “AIDS patients”, I find that is rather irrelevant—we are only concerned with the fact that they tested positive for HIV. If HIV doesn’t strongly cause AIDS, but medication does, then of course we shouldn’t expect these medication refusers to progress into AIDS and become AIDS-patients, which is exactly what the study is showing. So I dont’ understand why you are trying to show that they are not AIDS patients—that’s the whole point! You may be unknowling arguing for the opposition (or perhaps I am confused on your position or you have none).
All of this is consistent with the CDC statistics underestimating the general transmission rate. You write that the rate estimated from the European study “agrees with” meta-analyses of 1st world data, and that the 3rd world rate estimated by meta-analysis is higher still. So pooling the two meta-analytic results gives a global average rate greater than the 1st world average rates, i.e. averages greater than the CDC rates.
I don’t think I am dismissing these studies and the work. The bit of my comment you’re quoting refers, after all, to secondary analyses in one of those studies. The point I’m trying to make by drawing attention to those analyses isn’t something like “look, the transmission rates are higher if you don’t use condoms, clearly they’re high enough for HIV to spread through the population”, but instead “associations between condom use and transmission rates, and between sex during menses and transmission rates, have a far higher likelihood in a model where HIV is an STI than in a model where it’s not”. It’s much easier for me to explain why having sex with a woman at particular times in her menstrual cycle would correlate with HIV transmission if I presume HIV’s sexually transmitted, which I interpret as evidence for [edited: I had a brain fart and originally wrote “against”] the view that HIV’s an STI.
Don’t worry, I’m not. I’m suggesting that because the sampled people all come from the same small geographic region, it’s possible that genetic resistance and/or weaker HIV variants are more common among them.
The specific evidence I have in mind is the geographic restriction of the sample. A group of people from one place will tend to be more genetically similar than a worldwide sample, and will be more likely to share strains of a disease. I expect HIV-1 variants do spread diffusely in subgroups, but I don’t think that rules out my point. Particular alleles of genes spread throughout humanity, but spatial proximity still correlates with genetic similarity among people. Sure, geographic restriction is hardly strong evidence of these things — a sample of people who live on the same street could quite easily contain just as much variety in genes that affect HIV resistance (or variety in HIV substrains) as a wider sample. But with geographic restrictions, the variance is likely to be less. (Notice also that the sample seems to be relatively racially homogeneous — only one of the 36 cases is described as black. That’s more evidence of less genetic variance, though very weak evidence, as racial groupings don’t represent much genetic variance.)
Yes, but you originally presented the study as “data very close to what [I am] proposing”, and part of my proposal was that the study’s subjects “are followed up regularly” for 20+ years. Koehnlein’s study started in 1985, most of the subjects entered it in the 1990s or later, the latest update is from 2001, and the published report is from 2003. So most subjects don’t seem to have had anything like a 20-year (or more) follow-up.
The bigger question we’re looking at is whether HIV causes the complex of conditions we recognize as AIDS (and, before that, HIV transmission rates).
True, but the question is how much better than average their lifespan was, and the causes of death also matter. If the patients lived for many post-HIV years more than average, but most of them died of Kaposi’s sarcoma, I would strongly suspect AIDS.
It doesn’t mean the study is somehow wrong, but I see it as a warning sign. It’s very unusual for someone to spend 16+ years on a unique, systematic study of untreated HIV patients, and then not publish it anywhere except as a one-page summary in the middle of a review article that I suspect was mostly written by someone else. I have a hunch that Koehnlein’s unable to get the study published in full.
I can think of two reasons why it’s very relevant. First off, if most of the subjects didn’t have AIDS, that might well explain why their death rate’s less than that of AIDS patients (and Duesberg & Koehnlein quite explicitly compare the sample’s death rate to that of “German AIDS patients”) — one dies of AIDS instead of HIV per se, and it normally takes years to go from being HIV+ to having AIDS. Secondly, Duesberg & Koehnlein say the study is of “AIDS patients”; if it turns out that there are people in the study who didn’t have AIDS, D&K have made a specious comparison, and a false claim about the nature of the study. That would raise questions about how much I should trust their report of it.
Agreed, with the proviso that one would have to wait a long time to be sure that HIV didn’t eventually progress to AIDS.
Disagreed. If you’re agreeing with my suspicion that some of the people in Koehnlein’s study didn’t have AIDS, you’re implicitly accepting my guess that the clinic symptoms and CD4 counts in the table are those observed for each subject when they entered the study, because that forms the basis for my suspicion. And if you believe that, it follows that you can only infer whether a subject had AIDS when they entered the study, and not whether they later developed AIDS.
Well, it’s possible I am. But see above!
For a variety of reasons, I find it useful to separate the two, and the 1st world rates are the most important—the virus outbreak started in San Francisco essentially (following the end tail of the massive hippie/drug liberation social experiment). Also, the 3rd world rates are suspect in general, as one of the meta-studies notes, for a variety of reasons. And regardless, even the 3rd world rates are 30 times lower than typical STD’s, even if they were accurate (which is dubious).
Yes, but as you admit,
So at this point I think it is more time profitable to switch gears and spend a little effort investigating other LTP reports other than this single study. And just a little google searching shows that there appears to be now a number of other LTPs from across the world that are similar to the Koehnlein group—and avoiding traditional treatment appears to be a common link. You can google it as well, but here are some links:
from an article in Health Care Industry (older − 2000):
A 2005 NYT story about a LTNP:
And finally here is a compilation of another dozen studies or cases of untreated LTNPs (older hasn’t been updated recently)
So it doesn’t look like the Koenhnlein study is an isolated incident. I am still looking for more recent studies or follow ups.
From everything I know so far, the vast majority of patients were treated, so if treatment has a beneficial effect at all, then it follows that the ratio of treated LTNPs to untreated LTNPs must be equal or greater to the original treatment ratio. I understand that in the west that treatment ratio was very high, probably > 95%
And as far as I can tell, we aren’t seeing anything like that ratio in LTNPs, so this could be very strong support indeed for at least part of the Deusberg hypothesis: that the treatment can itself cause the disease.
Edit: I completely guessed on that 95%, and later found this telling quote in the NYT article (I am reading these as I go):
But what it would really need is a big long term study with the sampling precommitted early based only on choice of treatment strategy. Actually, this should be how our entire medical system works in general. If the drug companies produce a treatment like AZT, doctors and patients get to choose treatment strategies, and overall mortality data is collected slowly over time. Survival of the fittest strategy.
I should have said here “what the study intends to show”
I was under the impression they tested them when they entered the study and then periodically thereafter just as you’d expect. The overall concern is the long term result—the death rate. I thought the entire point Deusberg was making was that overall mortality was lower in this untreated group than in the general treated population, and the medications themselves were actually causing AIDS progression.
As I understand things, HIV jumped into the human population in Africa decades before hippies and the 1960s counterculture, and that only after being established in West/Central Africa did it reach the US. As such, the 3rd world transmission rates have just as big a role to play as 1st world transmission rates. With an external pool of infected people established, it became possible for HIV to be reintroduced to the US over & over again until it landed in US subpopulations that spread it with needle sharing & frequent anal sex.
Without being more specific about what’s wrong with the rates, I’m not sure why this means the 3rd world rates are necessarily about equal to (or less than) the 1st world rates. At any rate, HIV is not a “typical STD”, and a lower transmission rate than other STDs doesn’t mean much as long as HIV’s rates are sufficient to enable its spread. Also, Wei_Dai suggested that the P/V sexual transmission rate for HIV is comparable to that of genital herpes, a point you didn’t seem to dispute in your reply. Do you believe that genital herpes has too low a transmission rate to be an STD?
But here’s the thing: the lone fact that a case report or study has some LTNPs doesn’t necessarily mean much in terms of questioning the HIV-AIDS link. For example, the studies in the 2000 Research Initiative/Treatment Action! article (I think “Health Care Industry” is just the name of the section on findarticles.com where the article’s mirrored) seem to focus on gathering together people already known to be treatment-refusing LTNPs, and finding out what makes them LNTPs. Simply observing that treatment-refusing LTNPs exist doesn’t convince me. Even if 99% of HIV+ people progress to AIDS within some time frame, with so many HIV+ people there are going to be a lucky few who turn out to be treatment-refusing non-progressors.
By contrast, Koehnlein’s methodology seemed to be different, which was why I initially thought that work might be compelling. I’d assumed that Koehnlein systematically recruited people into the study when they originally tested HIV+, not later, which would prevent Koehnlein gaming the study by excluding non-LTNPs. (Of course, with all the questions I now have about the study, I’m questioning even that. D&K don’t say when the subjects were recruited into the study, only when they were diagnosed HIV+. Possibly Koehnlein recruited subjects years after their HIV+ diagnoses.)
The catch with those 14 reports (the last of which is just a second-hand anecdote) is the same as for the other ones you linked: the page listing them doesn’t say what their sampling strategies were, and I think it’s likely that a lot of the reports’ authors deliberately sought out treatment-refusing LTNPs instead of representative samples. (The list is probably also a selective one, considering the website hosting it.) For example, the first report in the list is “based on 10 HIV+ people” who didn’t use antiviral drugs. I find it unlikely that doctors would bother publishing a study of only 10 LTNPs if those people had taken antiviral medication; it wouldn’t be very informative. It’d effectively be a tiny drug trial, and there are already far bigger trials of anti-HIV drugs. So I’d guess the doctors’ aim was to deliberately search for as many treatment-refusing LTNPs as they could find, because other doctors have something to learn from how their bodies work. If so, it wouldn’t be surprising that they found a handful.
That only follows if there aren’t any confounding factors associated with treatment status. If (making up an example here) HIV+ people being treated use treatment as an excuse to resume risky behaviour, and the treatment is only marginally effective, we might well end up with relatively few treated LTNPs. (I haven’t looked into this. Maybe it turns out that there aren’t any major confounding factors, but I wouldn’t want to assume them away without evidence.)
If you’re basing this on counting reports of LTNPs, you might be getting a skewed picture, since treatment-refusing LTNPs are much more newsworthy than LTNPs who accept treatment, and the latter probably don’t get so many of their own journal articles and magazine profiles. To count them, you’d probably have to locate reports of HIV drug trials that happen to have data on how the testees progress.
It usually takes several years for HIV to progress with AIDS, with or without treatment. So it wouldn’t be that surprising if there’s a large minority of people who don’t develop AIDS within a decade of HIV infection, and a fair few of them are probably, yes, medicine-free. (Plus, of course, we’re looking at a newspaper’s paraphrase of something a scientist said, so I’m inclined to exercise caution.)
To be honest, I think D&K are confused themselves about what the study’s meant to show. D&K call it “a study of AIDS patients”, but then they write “our relatively small sample supports the hypothesis that without anti-HIV drugs and/or recreational drugs HIV fails to cause AIDS.” But if the subjects were all AIDS patients, how could the study show that they failed to progress to AIDS? They would already have had AIDS!
If you’re correct that Duesberg’s intent was to make the point “that overall mortality was lower in this untreated group than in the general treated population, and the medications themselves were actually causing AIDS progression”, then he’s trying to have it both ways. He can’t infer the first thing (lower mortality) unless the study subjects are AIDS patients, because other AIDS patients are his comparison group, and he can’t infer the second thing (medications causing AIDS) unless some of the subjects aren’t AIDS patients.
Also, I doubt Koehnlein did systematically test the subjects periodically for AIDS. CD4 counts are missing for some of the asymptomatic patients, and to test them for AIDS, they would have needed CD4 counts. So either Koehnlein didn’t have their CD4 counts (which implies that Koehnlein wasn’t periodically testing them for AIDS), or Koehnlein’s selectively withholding CD4 counts (and something funny’s going on).
Whew. The more I go over this study, the more worrying it gets.
Ah, unfortunately this got too long, so I had to split it.
I think this was a confusion of terminology, and “AIDS patient” in the general sense was used to just refer to all HIV+ patients he was treating. It did not refer to only a subset that had later stage ‘AIDS’ symptoms. At least, that’s how it read to me.
From what I understand, Koehnlein somehow found a way to treat patients without antivirals legally, so patients seeking non-antiviral treatment came to him. His ‘study’ is just a record of all such patients, when they first came under his care, their backgrounds, and eventual prognosis (a couple of deaths out of thirty or so patients so far).,
Koehnlein may subscribe to the Duesberg hypothesis, and as such wouldn’t place any special value on persistent tracking of CD4 counts.
It might be for the best! This splits the Koehnlein study discussion and the general HIV discussion into their own separate subthreads.
Yes, we initially read the phrase differently. I originally interpreted it at face value, figuring that in a review article about HIV & AIDS, D&K would take care to avoid confusing having AIDS with being HIV+. I now think I might’ve given them too much credit.
Nonetheless, at one point, D&K must be using “AIDS patients” with its narrow meaning (patients with AIDS proper) and not its informal one (patients with HIV who may or may not also have AIDS), because the statistics they quote for German AIDS patients match the Robert Koch Institut’s AIDS statistics, but not the organization’s HIV+ headcount.
Whatever D&K’s intentions or confusions, my earlier point that the study can’t provide strong, simultaneous support of all the conclusions drawn from it still stands.
If so, Koehnlein’s testing his (her?) own definition of AIDS, not an orthodox one, and all bets are off.
That’s a theory, but it has some critical flaws. Namely one must wonder why did it not spread via prostitutes, needle sharers and blood transfusions earlier? Condom use dropped with the adoption of the pill in the 1960′s and the sexual liberation opened up a hetero transmission channel which has about the same net transmission rate (always limited by the insertive step).
AIDS became an epidemic in San Francisco in the early 80′s, and it grew quickly from a handful of cases to effect a large portion of the gay population, and was closely correlated with a diverse number of fundamental lifestyle differences. It is this phenomena, this quick sudden outbreak in a very specific subgroup, which I find extremely difficult to reconcile with the transmission data. Tops and bottoms tend to specialize so the rate-limiting factor for expansion in the gay community would be closer to the insertive A rate, at around 0.06% vs receptive at 0.5%. Needle sharing is about 10 times more effective, and blood transfusion is around 1,000 times more effective.
But all the early cases are in this one specific group, which is not even the highest risk group. I mean, the transmission rates for insertive V and A are about the same, and there are far more heteros than homos, so it just doesn’t make any sense. And don’t tell me the homos are having all the sex—they may be having more individually, but not when considering prostitutes and sexually liberated women in the 60′s and 70′s, the fact that heteros have anal as well, and the 100 to 1 hetero to homo ratio. The overall hetero transmission channel is much much larger, especially after considering needle sharing and transfusions, and yet the disease only appears in the homo subgroup, time and time again. Why?
Ignore for a second all high level conceptions about HIV. Don’t privilege the orthodox HIV hypothesis, instead compartmentalize and consider just this evidence concerning transmission rates, and how that evidence should cause one to update from an initial 50⁄50 split between two alternate hypotheses:
HIV spreads primarily horizontally and is novel in homo sapiens
HIV spreads primarily vertically and has been in homo sapiens for a long time
The transmission rates clearly favor 2 - the virus can barely spread sexually, but can spread fairly easily antenatally.
Also, if you actually read into the depths of these studies, it becomes clear that there is a strong framing bias to favor the default sexual transmission theory. The actual sexual transmission rates are not known with certainty, and all of these studies depend on the orthodox HIV model. The actual horizontal transmission rate may be . .. zero.
One of the more interesting hetero sero-discordant studies is the Padian 10 year study. Trying to isolate for hetero sexual transmission, they actually strictly eliminated all drug users by using actual drug tests—something that others have not done to my knowledge. They then did the typical questionnaire analysis trying to determine how each seropositive index member in the couple actually caught HIV—which is more or less just a random guessing game, and then they applied regression techniques to look for risk factors.
The risk factors they found are more or less random, and do not point to a sexually transmitted disease. For instance:
So large amounts of unprotected sex did not appear to be a very significant risk factor. The highest risk factor was just anal sex as a practice, not the number of contacts.
But what was really interesting in this group of some 600ish hetero non-drug users was that during the length of the study, there was not a single seroconversion, even though condom use in these couples was imperfect:
There is zero evidence that non-drug using heterosexuals acquire the disease sexually, and studies such as this are evidence favoring a vertically transmitted virus.
Why does it only spread laterally into gay men and drug users, even though this is extraordinarily unlikely if it truly is horizontally transmitted?
I haven’t analyzed genital herpes and know very little about it, and regardless it is irrelevant. If the data says that HIV can not be sexually transmitted, and another disease has the same epidemologial data and is also called an STD, that somehow doesn’t magically change the data. It just makes both classifications wrong.
Simply observing that treatment-refusing LTNPs exist doesn’t convince me. Even if 99% of HIV+ people progress to AIDS within some time frame, with so many HIV+ people there are going to be a lucky few who turn out to be treatment-refusing non-progressors.
There is no ‘luck’ and it all depends on the ratios. If only 1% of HIV+ people refuse treatment, but even just 10% of all “long-term non progressors” refuse treatment, then clearly treatment itself is part of the problem.
It is strange and interesting that you think the cofactors only could work in favor of your privileged hypothesis. There is also the placebo effect to consider, and in a drug trial that is not double blind (as the AZT trials could not be) those who found out they were getting placebo believed they were going to die, and that encouraged wreckless behavior, not the other way around. Also, all the reports on LTNPs I have read are unanimous on lifestyle change being a distinguishing factor- reduction in drug use and bathouse type partying, general increase in healthier behavior. However, they still die at accelerated rates, and some eventually get AIDS.
Overall though it is pretty clear that even with some placebo benefit in it’s favor, AZT had no net benefit. If one could factor in the placebo bias, I expect it actually increases mortality a little on the whole. However, the data on the original AZT trial and later the more extensive concorde trial show that AZT has little effect or a small net negative effect. I think it is difficult to pin all of the modern deaths on AZT, and clearly AZT was not the main killer during the trials, but the fact of the matter is we simply do not have a control group to compare to in the long term.
This is the first cohort to basically be on sustained chemotherapy for life. It’s hard to imagine that this could not have negative long term effects.
Looks like I have to split a comment too!
I’m not sure which specific time period you’re referring to with “earlier”. If you’re talking about the 1970s, I’d guess it’s because HIV simply hadn’t been introduced to those subpopulations often/early enough to stick. If you’re talking about the early 1980s, well, it looks like HIV did spread, at least among needle sharers and people who had blood transfusions. (I haven’t seen data on prostitutes.) According to this 1985 Science article, 12,932 AIDS sufferers were reported to the CDC by August 30, 1985. 1.5% of them had received blood transfusions within 5 years of diagnosis, and 17% were heterosexuals who’d used IV drugs. (Also, 12% of the homosexual & bisexual men diagnosed were IV drug users.)
Although I’m sure tops & bottoms “tend to specialize”, I doubt men with dozens of sexual partners are completely picky about which role they play. If men are inconsistent about being the top/bottom, the insertive anal transmission rate is going to be an underestimate. In fact, it’s likely to be an underestimate twice over, because preexisting STIs make transmission more likely, and promiscuous men will have more STIs on average. You’ve also got the handful of IV drug users among these men. If I’d had to bet on where HIV would rear its head first, the bathhouse subculture would’ve been a great choice to put my money on.
But neither of those can have an impact until HIV’s introduced to the subpopulations of needle sharers/blood donors, and even after that, their effect will depend on when HIV reached those subgroups, and how many people in those subgroups start off with HIV.
Only if you define “early” as really early: the first reports of IV drug users with AIDS came out in the same year as the first reports of AIDS in gay men. And again, risk isn’t everything. Even if group X has much higher transmission risks than group Y, if the virus reaches group Y first, the earliest infections are likely to emerge in group Y.
While the receptive A rate is higher than the receptive V rate.
Ease of person-to-person transmission within a subgroup matters more to how quickly a disease spreads through that subgroup than the subgroup’s absolute size.
Which increases the ease of transmission.
Which doesn’t much matter if there’s hardly any HIV among those women to start off with. I’d also guess that the proportion of “sexually liberated women” having as much sex and injecting as much drugs as gay men in the 1970s/1980s bathhouse culture is relatively small.
As often as promiscuous gay men?
See above about subpopulation size.
To extend your own metaphor, the “hetero” channel was wider than the “homo” channel, but the “homo” channel had faster flow. Plus, again, there were gay men who engaged in IV drug use, and if gay men were among the first US citizens exposed to HIV, as is very possible, that would’ve given them a head start.
Not sure what that means specifically.
It’s the hypothesis favoured by the medical establishment and the scientific mainstream on the basis of evidence that is at least circumstantial, and at best definitive, which suggests it’s a good starting point. I’m not plucking an arbitrary hypothesis to defend out of thin air.
I really disagree with how you’re framing things here. It’s screwy to split horizontal transmission & vertical transmission into separate hypotheses, since both processes are happening right now throughout the human race, and both processes happen at different rates across time & place. I don’t understand why the mode of transmission corresponds to how long HIV’s been circulating in humanity, either.
Mother-child HIV transmission rates per child (without anti-HIV prophylaxis) are generally higher than sexual transmission rates per sex act, sure. But there’re a lot more sexual acts happening than childbirths. So there’s more to the situation than raw transmission rates.
There are several documented cases of early AIDS where we have stored tissue that later tested positive for HIV, such as the gay teenager who died in St Louis in 1969. This poses a serious problem for the standard theories that HIV is transmitted horizontally (unlike any other retroviruses) and presumably came out of Africa. So how did it get into this teenager? You would need some world travelling gay subculture at the time to link the disease to Africa, but not a big enough subculture to create an epidemic. Since only a small portion of men are gay, we should expect that if it came out of Africa the first vectors would have been heterosexual, not homosexual. And as there are several of these strange early cases, it would have had to come over from Africa multiple times, but always only in gay men. This theory is just not salvageable.
Also, consider that the different genetic subtypes are closely associated with particular risk groups—subtype M appears in MSM and IV drug users but not others, which doesn’t make any sense for a horizontally transmitted viral vector. Most of the subtypes are linked to particular geographical regions in Africa, which points to a long history in humans (with M representing a novelty linked to novel behaviour).
Also consider that all other primates have naturally occurring lentivirus family retroviruses very similar to HIV. Consider that the entire family of retroviruses are more symbionts than parasites—humans are ‘infected’ with thousands of different retroviruses, many of which are integrated into our genome, and they have functional roles in gene expression and even the formation of the placenta.
So if all other primates have naturally occurring lentiviruses, why don’t humans? There is a clear evolutionary niche for a lentivirus in mammals, and it seems odd that homo sapiens somehow lost their naturally occurring lentivirus at some point in our evolutionary divergence, only to re-acquire it very recently in the last one hundred years. It just doesn’t make any sense at all.
Retroviruses generally are not horizontally transmittable, and there is no evidence that HIV is an exception. The Padian study in the other thread branch directly shows that HIV is probably not sexually transmittable.
But most of the earliest confirmed AIDS cases were retracted (David Carr) or have a direct connection to Africa (anonymous Congolese adults & Arvid Noe). It’s only Robert R. (the “gay teenager” you refer to) who didn’t have a direct African connection, but that doesn’t mean there wasn’t one, and such a connection wouldn’t even be necessary with Haiti available as a closer source of HIV.
This is one teenager. He only had to be unlucky once when having sex with just one infected man.
I’m confused. This PNAS paper presents good phylogenetic evidence that the HIV strains causing the North American epidemic came from Haiti, and that Haiti’s HIV came from Africa in the 1960s, which “suggests its arrival in Haiti may have occurred with the return of one of the many Haitian professionals who worked in the newly independent Congo in the 1960s”. So it’s Haitian economic migrants who would’ve been the “first vectors” to carry HIV out of Africa in any real number, and I have no reason to think they were disproportionately homosexual.
If by “strange” you mean that all those cases are inexplicable, I disagree.
Not at all.
I’m not an epidemiologist (or a geneticist), but couldn’t that just be a founder effect perpetuated by MSM and IV drug users transmitting HIV much better amongst themselves than they transmit it to everyone else?
I’m not seeing why this would be evidence for/against orthodox theories of HIV & AIDS. (And if I were being pedantic, again I’d suggest the relative insularity of MSM and injecting drug users as why subtype M’s linked with them, rather than the novelty of their behaviour as such.)
I’ll pass on commenting on your last three paragraphs, since what I know about retroviruses would fit on the back of a postage stamp. I will try checking Padian et al. again, though.
Yes, I don’t know any other studies that used direct drug tests. There is this Madrid study of heterosexual transmission that used indirect testing of “markers related to drug addiction (e.g., hepatitis C serology)” to check for drug use in addition to questionnaires, and its recorded transmission rate is quite high: 26%, out of 38 couples. However, it looks like a retrospective study.
Although quantity of sex doesn’t seem to have made much difference, the unadjusted odds ratio associated with not using condoms bordered on statistical significance with a confidence interval of 0.95 to 3.01. After adjusting for the number of sexual contacts, that odds ratio went up to 2.1, becoming significant and equal to the adjusted odds ratio associated with anal sex. I notice too that after adjustment, STI history — a risk factor elsewhere associated with HIV transmission — was the risk factor with the highest odds ratio.
It would be more interesting if the relevant sample did contain 600 heterosexual non-drug users followed for the length of the study. However, the “no seroconversions” result comes from the study’s prospective part, which involved only “175 HIV-discordant couples over time, for a total of approximately 282 couple-years of follow-up [...] attrition was severe”. That’s a mean follow-up time of only 19 months per couple. Most couples probably got less follow-up time than that, because severe attrition would tend to negatively skew the follow-up time distribution, depressing the median.
That’s not all. The investigators didn’t just counsel the couples on safe sex, but also set up a 24-hour telephone support line, a newsletter and regular meet-ups. These measures were very effective in changing the couples’ behaviour: by the final follow-up, 15% of the 175 couples abstained from sex and 74% used condoms. So, at final follow-up, only 11% of the couples — nineteen in absolute terms — were at substantial risk of HIV transmission. The study’s statistical power to detect the small (in absolute terms) risk of heterosexual HIV transmission wouldn’t have been that great, especially given “the lack of incident STDs during the course of the study” (page 355).
You’re exaggerating. Even ignoring all other work on HIV’s epidemiology, there’s evidence of heterosexual HIV transmission in this very study! Its prospective aspect is just half of the research; there’s also the cross-sectional sample, which includes 230 couples recruited after the researchers began screening subjects for drug use in 1990. HIV transmission occurred in this subgroup, and after adjusting for estimated number of sex acts across the entire cross-sectional sample, there was no association between being enrolled before 1990 and HIV transmission (adjusted odds ratio = 1.0, 95% confidence interval = 0.98-1.0), so the transmissions in the cross-sectional group can’t just be attributed to the pre-1990 (i.e. unscreened) subgroup. (And again, recall the higher odds ratio for failing to use condoms and having a history of STIs. That sounds like more evidence of sexual transmission to me!)
But...it doesn’t only spread laterally into gay men and drug users?
That’s true!
Or your definition of an STI too restrictive.
I think you have some implicit assumptions there to unpack.
Do you have references for this?
Well, I expect that helps. (Which is not to say that switching to a healthy lifestyle halts the progression into AIDS.) I can’t imagine doing poppers and having casual sex is a good thing for anyone with HIV. (Come to think of it, isn’t it possible for someone who already has HIV to reinfect themselves with other substrains and make their infection worse?)
Makes sense.
I think I’ll hold off on commenting on the last couple of paragraphs about AZT since (1) I really don’t know much about AZT, and (2) this discussion is becoming quite extensive and too much of a time sink for my liking.
Ok, so concerning the Padian study, I believe you have misread it, and I am to blame because I originally mislabeled it when I said:
I was wrong—it was not in fact a study of sero-discordant couples, and I apologize for that mistake, for it seems to have mislead you. This is evident in the abstract and is explicitly clarified elsewhere:
So they recruited non-drug using heteros of either sex who had steady partners, and some fraction of those partners were already infected—specifically 19% of the female partners and 2% of the male partners. They explicitly state there were no new infections in the abstract:
And again later:
The last part happens to be in the ‘prospective results’ portion (where they switched focus to only serodiscordant couples), but should not be interpreted to somehow only apply to the post 1990 time period—as it says “after entry into the study”, and agrees with the “no new infections” in the abstract.
So I believe you have misinterpreted when you say:
There was not a single new infection (seroconversion) during the entire ten years across all couples.
You are correct that they were counseled on condom use, but this does not seem to have influence actual reported condom use, even though the percentage of couples using condoms upon entry increased from around 50% to 75%, a significant fraction reported inconsistent usage:
So the key of this study and really all of the heterosexual transmission studies is that it is all just guess work. The 19% female and 2% male seropositive partners were just assumed to have acquired HIV sexually, but as this occurred prior to the study, the drug controls were not in place (and testing didn’t start until 1990). They are just assuming sexual transmission in these cases based on the strong unfounded assumption that HIV is sexually transmittable, they really have no idea.
What they did show, was that over about 4000 couple years, there was not a single new transmission in this drug-screened hetero sample. Using the 75% consistent condom use number, lets say then 1000 couple years of inconsistent usage, and perhaps then taking that to conservatively imply 80% condom usage on average for ‘intermittent’ users, you still have 200 couple years of unprotected sex, and not a single transmission. Remember that most of the partners (80%) are female, some practise anal, and that condom usage was reported as highest only for female index patients (male partners—paradoxically). Also, condoms are not at all 100% effective, even when used properly.
If there had been just a single seroconversion, that would correspond to a rate of transmission of 1 per 200 to 1000 years of sex, or perhaps a rate of 1 in 20,000 to 1 in 100,000 sex acts − 0.01 to 0.05%. But that single seroconversion did not happen. The actual transmission rate was exactly zero. As this study actually controlled for drug use cofactors it is the most accurate data I’ve seen for actual sexual transmission, and it shows that most studies grossly overestimate sexual transmission—the reality is there is no M->F transmission or it involves iv drug use.
The problem is simple—as untreated HIV presumably leads to death in 5-10 years, it needs to infect more than one person on average in that timespan just to maintain HIV population rate. To achieve a doubling in 10 years, it would need to infect 3 new people on average in that time.
To explain the growth rate in the early 80′s requires an absurdly faster doubling rate. This is not an STD. It is something else.
Agreed. I need to stop thinking about this.
Alright, I’ve had another look at Padian et al.’s paper. I did follow your lead in thinking the study was solely of sero-discordant couples, and I agree with you now that it actually wasn’t. However, the relevant part of the study is the prospective sample, which was solely of HIV-discordant couples, so my overall interpretation of the study’s nominally zero transmission rate remains unchanged.
Right, but Padian et al. refer to the retrospective part of the study as the “cross-sectional” part (see page 351: “the retrospective nature of the cross-sectional aspect of our design”), implying there was no follow-up in that part. Without follow-up, they couldn’t have detected seroconversion after entry into the study, so the retrospective method wouldn’t pick up on post-entry transmissions however often they actually happened. So it’s a mistake to argue that no transmission happened in the retrospective group on the grounds that no transmission was observed, because the retrospective method can’t detect new transmissions.
So, although it’s technically true that the “no seroconversions” result applies to the whole period of the study, it would’ve been disingenuous for me to say so, because the researchers could only spot new seroconversions from 1990 onwards.
The study’s non-prospective part was incapable of detecting post-recruitment seroconversions, so the basis for the “no seroconversions” result is indeed the prospective part.
Well, there might’ve been new infections between 1985 & 1996 among the retrospective sample, but the study wouldn’t have detected those. The retrospective method would only detect those that happened in a couple before they entered the study.
The fact that a minority of the couples still didn’t use condoms consistently at their final follow-up doesn’t mean the counselling had no influence!
Only for the retrospective sample.
The calculations you do in the next couple of paragraphs seem to be based on both the retrospective & prospective subsamples, which exaggerates the number of couples in which new HIV transmissions could have been observed. New transmissions would only be observable among the couples in the prospective group.
So let’s run the numbers again for just that group. That group had 282 couple-years of follow-up, just 7% of your starting point of 4000 couple-years. Multiplying your final unprotected sex estimates by 0.07 gives me just 14 to 70 couple-years of unprotected sex.
Following on from that, how likely was a seroconversion for some hypothetical transmission rate? Let’s take 0.05%; 0.1% is unusually high for heterosexual couples, if I remember rightly, and 0.01% feels too low. Supposing the couples had 100 sex acts a year, we have (with a lot of simplifying assumptions) 1400 to 7000 sex acts. With 7000 acts at 0.05% a time, I get a 3% chance of no seroconversions. With 1400 acts, I get a 50% chance. This suggests that the likelihood of no seroconversions was not insignificant, so inferring a transmission rate of zero is likely to be a type II error. I also haven’t accounted for the 15% of prospective subgroup couples who became abstinent during the study.
Not with this lack of statistical power it doesn’t.
Whaaa?! Wouldn’t that imply that every female partner who became seropositive in the other studies got infected from secret lesbian sex or injecting drugs?
I don’t see that as a prohibitively high barrier. Especially because there’s not really just one transmission rate for each kind of sex act: transmission rate is moderated by other factors like stage of HIV infection, being infected with other STIs, and so forth.
The early 80s growth rate wasn’t just driven by heterosexual sex.
There was follow up starting in 1990. Basically they started the study by recruiting in 1985 and were originally focused on the retrospective aspect. Couples come in, fill out a questionairre and they attempt to screen out drug users and look for patterns in infected partners (couples where both are seropositive). Then in 1990, they began bringing couples in for examinations and follow up tests—“Physical examinations for both partners were initiated in 1990.” This is the beginning of the prospective part, but it doesn’t mean it is only valid for couples starting after that date, which comes from the very first sentence of the abstract:
The prospective part was not limited to only couples enrolling after 1990. That is only the beginning of the biannual checkups.
Technically yes, but immediately in 1990 on the first follow-up they would have spotted any new seroconversions in any serodiscordant couples currently in the study. And they would have clearly mentioned any such detected seroconversions, and indeed they clearly mentioned that they detectected exactly zero.
But regardless, yes I did botch the total couple-years. The text implies that the 175 couple group with follow up was the total set of persistent couples:
Abstenence was between 0 and 14.5%, consistent condom use betwen 32% and 74%, and anal between 37 and 8%. We should probably also factor in that condoms are not 100% effective. Lets ignore that for a second and assume midpoints of the above numbers, with around 100 sex acts per year, or 10 per month. If ‘inconsistent’ means ~50%, I get ~2 unsafe acts per month, or ~6,000 unsafe acts. The majority of these couples (80%) are male seropositive, so the higher M->F numbers apply 0.1% to 0.5%.
The infection rate for P->V is supposedly 10 in 10,000, or 0.1% according to the CDC from the European study. The infection rate for P->A is supposedly 50 in 10,000, or 0.5%.
Sure it would have been better with 10,000 couples over many years, but how much specific negative evidence for sexual transmission does one require? Is there any specific positive evidence?
There is a larger set of data Deusberg points to for lack of sexual transmission, which is the hemophiliac population, around 75% of which tested positive for HIV in the 80′s. There were about 5,000 wives of HIV+ hemophiliacs, and the CDC reports 131 were diagnosed with miscellaneous AIDS diseases between 1985 and 1992. However, the particular diseases were age-related opportunistic infections, including 81% pneumonia—no KS, demantia, lymphoma, or wasting syndrome generally characteristic of typical AIDS. The 131 / 5000 appears to just be regular background rates for those illnesses. If AIDS was sexually transmitted, we should have seen evidence in this population of wives. Many of these couples were having sex for years before the blood was tested. This strongly contradicts any theories of a sexually transmitted etiological agent.
And if it is not sexually transmittable, then it is either only vertically transmittable or the entire theory is hopelessly flawed at a deeper level. I suspect the latter because the measured vertical transmission rates are not high enough to sustain plausible viral population.
Not at all—the data just shows that seropositivity is not sexually transmittable. A great deal of other evidence, combined with this clear lack of sexual transmission shows that seropositivity is clearly linked to risk groups with immunosuppression in general.
What you’re saying about Padian et al. just clicked for me. I’d got it into my head that they were allocating each recruited couple to either a retrospective track or a prospective track, with couples switching from the retrospective track to the prospective track after 1990, but without their data being carried over. But you’re saying the couples already enrolled in the study pre-1990 were automatically entered into the prospective part with their earlier questionnaires & lab work retained, right? That’d make more sense than how I first interpreted the paper. (Serves me right for skipping the abstract and diving straight into the methods section. Twice.)
Alright, let’s crunch some numbers.
Using the midpoints of the ranges is a good first guess in the absence of other information. However, I think there’s a good reason to use estimates much closer to the follow-up percentages (14.5%, 74% & 8%) than the baseline percentages (0%, 32% & 37%). The prospective results section says that “approximately 97 percent of behavior change was reported between baseline and the first follow-up visit”. That is, when couples started/stopped using condoms consistently (or abstaining, or having anal sex), they almost always did so before their first follow-up visit, suggesting the couples changed their behaviour shortly after counselling, not gradually. If so, then the baseline percentages only represent the couples’ behaviour distribution for a few weeks; after that, the distribution would be much better represented by the rates at final follow-up.
This could have a big impact on the surprisingness of the zero seroconversions result. Switching from the midpoint rates to the final follow-up rates boosts the abstinence rate to 14.5% and the consistent condom use rate to 74%, while cutting the “[a]ny anal intercourse” rate from 22.5% to 8%. So the neither-abstinent-nor-consistently-condom-using rate sinks from 39.7% to 11.5%. Carrying that forward, I get an unsafe act count ≈1600 instead of ≈5600 (assuming 50% condom use in that 11.5% of couples).
That of course makes a big difference: with a 0.1% risk per act (and I’d peg the risk as being far closer to 0.1% than 0.5%, given the low rate of couples admitting to any anal sex, let alone repeated anal sex), 1600 sex acts have a 20% chance of not causing any transmissions, but 5000 sex acts have only a 0.03% chance. Evidently the unlikeliness of getting no seroconversions under a hypothesis of low-but-nonzero transmission rates hinges on the numerical assumptions made about sexual behaviours. (And there are yet more tweaks one could make to the numbers: whether to adjust for the couples that were female HIV+ instead of male HIV+, how much to adjust for condom unreliability, how much to adjust for the time lag between HIV infection and showing up as HIV+ on a blood test, and so on.) A claim that HIV isn’t an STI is a hefty claim to hang on this single result.
If I’m remembering correctly, the only pieces of specific negative evidence I’ve seen cited here were the transmission rates’ small sizes (which I don’t see as evidence that HIV isn’t an STI, because the fact that a number is small doesn’t mean I can safely assume it’s nil), and the zero seroconversions result from Padian et al., the strength of which is arguable.
I think the other studies of heterosexual transmission are at least suggestive. Explaining away the hundreds of female HIV seroconversions detected in those studies by assuming that each case of male-to-female transmission “involves iv drug use” does not seem credible to me. IV drug use is more common that it once was, but surely it’s not that common!
My scepticism is stronger still because a few of the studies have methodological features that would make transmission via needle sharing even less likely. I mentioned this Madrid study before. There’s also this ingenious study, which used sequence analysis on the subjects’ HIV samples to confirm that transmission was within pairs, making it less likely that non-index partners who seroconverted caught HIV from sharing needles with strangers.
It’s not as if these are the only studies that’re informative, either. This meta-analysis finds that male circumcision reduces HIV transmission risks, a conclusion bolstered by this randomized trial, a second randomized trial, and a third randomized trial. I’m not sure how I could explain these results without invoking sex as a way to transmit HIV.
Immunosuppressed or not, a person won’t get infected by a virus unless that virus makes it into their body. Even with immunosuppression as a cofactor for HIV transmission, it can’t substitute for HIV transmission.
I almost forgot to ask for a reference for this:
I’m unwilling to take Duesberg’s synopsis of these data on trust, and would want to see where he got his numbers from, and which methodological issues he might’ve glossed over. I can think of a few issues already, without even looking. The fact that the couples were having sex for years before getting tested in the 1980s wouldn’t mean much if HIV hadn’t been circulating in the blood supply for long. Different AIDS risk groups often have different constellations of AIDS-defining illness: Haitians often present with diarrhoea & TB, whereas US gay men often present with KS, for example, so I would guess haemophiliacs & their wives might have their own distinct AIDS-associated illnesses. Counting AIDS cases would underestimate HIV transmissions, because only some HIV+ wives would have progressed to AIDS. And so forth.
Also note this ‘ingenious’ study has an important point of evidence that does agree with the Padian study and points to a non-sexually transmitted etiology:
The circumcision studies from Africa don’t tell us much either, as circumcision is associated with ethnic/cultural groups and thus drug use and other factors.
There are other more parsimonious explanations that don’t rely on a ‘virus’ at all, and HIV—as far as it exists as a rather arbitrary collection of DNA/RNA sequences, may not be a virus at all. It could just as easily be trash RNA being secreted in exosomes tagged for immune system garbage collection. It could be regulatory RNA exosome messages intended for other cells. It could be a mutant form of an endogenous regulatory RNA exosome. It could be an endogenous ‘virus’ that forms as a cancer-like mutation of normal endogenous regulatory RNA exosome communication. And yes, it could actually be a true exogenous RNA virus that just happens to be remarkably similar to sequences embedded in the human genome (such as the so called “HERV” sequences) - and just happens to look like typical RNA exosomes in the microscope.
But even if it is a true exogenous virus that can jump between cells and that is a huge if, there is astonishingly little evidence it causes much harm.
There is a mountain of evidence that drug use causes harm, and specifically that particular drugs linked especially to the gay community cause specific types of chronic accumulated immune damage.
Methanphetamine (speed) and its derivatives for example is tightly correlated with HIV/AIDS, it is endemic in the “party and play” gay community, and we have a large amount of evidence that Meth does significant long term harm.
Firstly, Meth is a hyper-stimulant of the “flight or fight” stress response. This stress response essentially temporarily shuts down the immune system and digestion to focus the body on a temporary threat. A lion may kill you in a matter of minutes, while your body’s normal symbiotes/parasites such as fungal candida are not going to do much in this time frame—so stress is bad for the immune system, but this is ok because stress normally is temporary.
What happens when go on a multi-day meth binge and hyper-stimulate your stress response? Well, we don’t entirely know, but it appears to be pretty bad for your immune system. And finally, the drug itself has potential DNA damaging effects through oxidative free radicals. This is a particular problem for any drugs that are often heated up and burnt in either the consumption or production phases, resulting in oxidative byproducts. The typical crack-cocaine ‘cooking’ procedure is especially bad in this respect.
The ‘immune system’ - which really should be called the ‘regulatory system’, is second only to the brain in complexity. It is responsible for not only protecting the body from foreign invaders, but also for general regulation of symbiotes/parasites in the gut, identification and control of rebellions (cancer), as well as normal tissue generation and regeneration (healing).
The CD4 cell pathway in particular is especially complex, and these cells are responsible for identification and long-term memory of particular antigens. They go through an extensive selection process to eliminate possible identification errors (auto-immune disorders). This system is especially sensitive to DNA damage, which is happening all the time—and these cells are expected to stick around for many years to hold antigen memory. They also use a random DNA shuffling process early on to generate their antigen recognition system, and these cells are bouncing around constantly in the blood in such a way that makes essential complex DNA repairs—double strand break repairs—much more difficult.
Consider the insults that AIDS patients are inflecting on this system: known potent stress inducing immuno-suppressants such as Meth and Cocaine type drugs, and oxidized byproducts of cooked drugs directly injected or smoked. Also consider that the rectum is second only to injection as a route into the bloodstream, and associated with anal sex are lubricants which can be absorbed. Has anybody seriously evaluated the long-term health effects of anal lubricants? I haven’t seen such a study. Consider that earlier in the AIDS era more toxic oil based lubricants, possibly containing benzoprene deriatives, were more common. Fortunately presumably safer water based lubricants are more common today, as the oil-lubricants can destroy condoms. All of this stuff goes—right up into the bloodstream.
And finally we should look at gay related intestinal disorders—as most of the CD4 cells are actually in the gut, and gut problems are endemic in gay men. Whether it’s semen absorption, lubricants, or anal douching is unclear, but it appears to cause some chronic gut problem—and possibly leaky gut syndrome, allowing more foreign antigens to pass directly into the blood. Exposure to all these strange antigens may simply confuse the immune system. Now combine that with chronic meth use and you have a clear recipe for AIDS which doesn’t require a virus. Overall, the gut/immune system is designed for forward entry.
The hetero groups that get AIDS in the west tend to be hardcore drug users. The other known group is hemophiliacs. The “AIDS” each of these groups gets are quite different and really only have the low CD4 count and blood reaction test in common—which really are just general markers of a dysfunctional immune system. Hemophilliacs have a genetic disorder of the blood and never lived long until the AIDS era anyway, and injecting foreign protein for the clotting agent is immuno-suppressive in itself.
AIDS, like cancer, is something that anybody can get—but most will not progress to AIDS or cancer until they are already quite old, and will usually die of something else well before that. AIDS is really just a common immune disorder—the elderly often have it to some degree—lower CD4 counts and opportunistic infections. You can accelerate the aging of your immune system and progress to AIDS faster by chronic use of immune supressing hyper-stressors such as Meth/coke drugs and or direct toxic DNA damage through injecting or absorbing (anally) foreign matter into the blood.
None of this causes much immediate damage, but like smoking it ages particular vulnerable systems, probably through accumulated DNA damage, and this is why many people who quit eventually will progress to AIDS anyway a decade later or so—the damage has already been done, just as many smokers who quit will still progress to lung cancer at an accelerated rate.
But the insults that these risk groups are doing to their blood and lymph are considerably worse than smoking. Although notice there is a huge amount of overlap—someone who chronically smokes crack cocaine is much more likely to die of some lung infection than say karposi’s sarcoma.
Flicking to page 354 of Padian et al. I see this: “the practice of anal sex and lack of condom use have remained strong predictors of transmission since the beginning of the study”. And table 2 of the paper suggests that not using condoms is a statistically significant transmission risk factor, after adjusting for number of contacts (as I previously mentioned). I would not interpret that as agreement with a finding of “no significant difference”.
This argument might go through for observational studies, although even there I’d want a quantitative argument for why I should expect those confounders to have as strong (or stronger) an effect as circumcision’s apparent effect. But I also referred to three large randomized trials, and randomization reduces the association between confounders and treatment effects to statistical noise — that’s why people conduct randomized trials. So I still regard the trials as strong evidence for circumcision having an effect on HIV transmission; confounders don’t have a substantial effect on the results of randomized trials unless the randomization process was faulty.
(Incidentally, my original links to the 2nd & 3rd trials are now broken. Here are alternative links, although they may be paywalled.)
I’m skipping over the paragraphs on whether or not HIV is a virus since what HIV is specifically doesn’t bear on the point I was trying to make, which is that cofactors can’t subtitute for exposure to HIV (whatever one thinks HIV is).
Agreed.
Even if I grant you that, it doesn’t mean much to me unless one of those “specific types” of immune damage is the massive reduction in CD4 cell counts characteristic of AIDS. There are different kinds of immunosuppression, and it won’t do to presume that because something causes one kind of immunosuppression, it causes the kind of immunosuppression associated with AIDS.
At any rate, I suspect properly accounting for HIV+ status eliminates the link between whichever drugs you have in mind and AIDS. (Note that I am not denying any association between drug use and some form of immunosuppression — just non-spurious associations between drug use and substantial depletion of CD4 counts.) This 1993 Nature report describes results from the Multicenter AIDS Cohort Study. Check out the graph: there is a clear difference in CD4 count between seronegatives & seropositives, and only the seropositives suffer a downward slide in CD4 counts over the years, whereas differing levels of drug use show only meagre effects on CD4 count trajectories.
But how much does it affect CD4 counts?
But how much do they affect CD4 counts?
Skipping the background commentary on the immune system and the speculation about lubricants & intestinal disorders.
CD4 counts below 200-400 are AIDS’ key feature. The Nature paper I linked refers to “CD4+ T-lymphocyte depletion” as “the primary pathognomonic feature of AIDS”. Opportunistic infections of course vary in prevalence across subpopulations, but that doesn’t somehow negate the common symptom that allows them to get a foothold: low CD4 counts.
Do you have references for this?
But how much does it affect CD4 counts?
If they have HIV. Or idiopathic CD4+ T-lymphoctyopenia, come to think of it. Other than that...?
Hedging with the phrase “to some degree” makes that statement too vague for me to get a handle on, and it’d help to put a number on it. At any rate, CD4 counts don’t appear to be much lower among the elderly than among younger adults. A quick poke around for CD4 reference counts brings up this Mayo Medical Laboratories page, which gives a range of 424-1509 for people aged 18-55, and a range of 430-1513 for people aged 55+.
You can probably anticipate what I’d say/ask for the rest of the parent post, so I’ll save you the repetition.
You people are still going at it on the HIV thing?
This thread is now at 4.5*10^4 words (counted by copying into a text editor, and find/replacing to delete words that’re actually headers or vote/navigation links). I believe it should have been taken off-line at approximately the 5*10^3 word mark, if not sooner.
I admit I’m obsessively addicted. The more I look into it, the more I have found that HIV science has gone horribly, horribly wrong, and ‘HIV’ - whatever it is—if it even exists—is neither necessary nor sufficient to cause AIDS.
Considering that we have spent hundreds of billions of dollars on this hypothesis, this has larger implications for rationality and the scientific establishment in general.
This is absolutely true, and is a very good point. However, keep in mind that seropositivity is not a direct measure of HIV, and isn’t even especially correlated with HIV (see my reply in the other thread). Seropositivity is a rather good measure of CD4 cell decline—simply glance at that graph in the Nature paper and you can see that. Although I should point out I’m not sure if it’s actual cell loss that is measured or simply more CD8 expressing T-cells vs CD4.
Also note that there was no body of non-users of nitrates in the homo risk group in this study—they were split simply into ‘light’ and ‘heavy’, and the heavy users were twice as likely to get KS—I’d say that is a rather significant correlation.
This study has some flaws for looking at toxological causes though, as it was only looking at rather recent drug use (24 months), which is not quite the same as use history overall.
I’m not sure about Meth’s effects on CD4 counts in particular, but heavy cocaine use has a strong depleting effect on CD4 counts. First google result
But there are other factors in the homosexual risk group, the most important of which is simply semen. Semen is loaded with immunosuppressants that are designed to temporarily and locally deactivate the female immune system in the vaginal tract. One of those components are the prostglandins. It appears that evolution has struck a balance between semen’s need to disable immunity and the female’s need to regulate opportunistic microbes in the vagina (namely candida) - this balance sometimes fails and yeast infections result.
AIDS is in general associated with candidiasis—yeast infections—which overgrows in the rectal tract and eventually in the blood, and some of the seminal components absorb into the blood. Large-scale overuse of antibiotics to combat STD’s in the gay community is another significant cofactor, but semen itself may be a major part of the problem.
Many papers about semen’s immune suppression effects are a simple google search away—here is one typical example.
One of the most interesting though was this study of semen’s effects on rats from 1985.
They found that just seven daily rectal semen insertions had a marked immune suppression effect, but only in male rats, female rats didn’t seem to be particularly effected.
You seem to think that the CD4 count decline is somehow completely explained by HIV theory. It is not. The CD4 count decline is the defining feature of AIDS, but HIV’s role, if any, is theoretical and not well understood. So it makes sense to look at all the factors involved—for there are many independent immune suppressing factors in the primary AIDs risk groups—homosexuals and injection drug users.
In the original AIDS defining population of homosexuals, AIDS is associated with a tightly bundled set of cofactors:
passive anal sex
drug use
a history of a large number of past sexual partners and STD’s
a history of heavy antibiotic treatment
More on all the known immune suppressing factors in the gay cohort here. All of this needs to be taken into consideration before one starts chasing some new ‘virus’.
The drugs have changed over time (meth and MDMA being more popular now), but the correlation has remained.
The second significant risk group of AIDS patients appears to be injection drug users—really crack cocaine injectors in particular, and cocaine is known to deplete CD4 cells and cause AIDS all by itself.
I don’t know. Do you know? Do you want to investigate this? How? Keep in mind that before the AIDS era, hemophiliacs didn’t live all that long. We simply didn’t have much data on their longer term health problems. Then in 1985 the HIV panic mania spread, and the hemophiliac population was tested with Gallo’s “HIV’ test—which really is just a CD4 decline surrogate test. And we found that a big % of this population had declining CD4 counts and somewhat AIDS-like blood. What does this really mean?
And their wives don’t get it, btw. Neither do non-drug using prostitutes. Porn actresses in general do not appear to be at an elevated risk of developing AIDS either. None of this makes any sense for a sexually transmittable viral theory, but it makes perfect sense if AIDS is caused by primarily toxological chronic immune suppression.
I’m not so sure about that. I’m not sure that low CD4 counts in particular is common in the elderly, but compromised immune function is a typical problem of the elderly:
from the CDC: Opportunistic Infections in Immunodeficient Populations
“Opportunistic infections occur with greater frequency or severity in patients with impaired host defenses. Growing numbers of HIV-infected persons, transplant recipients, and elderly persons are at increased risk.”
“Elderly persons have defects in T-cell immunity that result in increased incidence and death from TB”
?
I won’t reply to this comment in full, but there’s a little loose end of my own making here, and I should tie it up:
“But how much does it affect CD4 counts?” (In response to the references to meth, cocaine, direct DNA damage due to injection and rectal absorption of foreign matter, and smoking.)
Strong claims shouldn’t hinge on a single study, but this study can be used to update probabilities for certain theories. You can think of it as eliminating possibilities.
Namely it eliminates or vastly reduces any hypotheses involving a typical STD transmission route. It allows for a very small possible horizontal transmission rate, but the most likely cluster is centered around zero. That doesn’t prove it is zero, it is just that this evidence strongly favors zero transmission rate theories over all others.
The what? I don’t think there is a single “female HIV seroconversion” to be “explained away” in any of those studies. From what I understand, and what Padian et al claim, the Padian study is the only properly controlled prospective study of heterosexual transmission. The other studies are just observational guesswork that are all circularly dependent on the notion that seropositivity is transmissible—they see a couple where both test positive and they just assume it was sexually transmissible—hardly anything resembling evidence for the theory—just circular logic.
First of all, in the other theories, there is no transmission to explain—and it certainly doesn’t have to involve iv drug use.
You have to understand what exactly seropositivity actually means. It is a blood test that was specifically designed to classify “aids-like” blood. Gallo developed it by comparing and testing a large amount of antibody combinations (biological IDs essentially), until he found a combination which successfully partitioned the AIDS-like and pre-AIDS-like blood from the normal blood. There are a host of other conditions that can cause full or partial seropositivity—think of it as a semi-general measure of CD4 immune malfunction. And actually, ‘malfunction’ is not even the right term, as one can test positive under some normal circumstances as well—such as pregnancy or during the course of some illnesses.
Testing positive multiple times, for no other apparent reasons, is a clear sign of some persistent CD4 immune malfunction which is highly correlated with full-blown AIDS in the future.
I glanced at the Madrid study and find it largely worthless compared to the Padin study. It is small, not properly controlled, and not prospective. They found higher “viral load” in couples that were both positive vs couples where only one partner was positive? That makes sense simply because as viral load loosely correlates with degree of sickness, we expect that to be correlated in couples. More sick people are more likely to not have partners at all or have sick partners.
You would see the exact same effect in smokers, and keep that analogy in mind when looking at any of this data.
Your “ingenious study” is not well controlled for drug use, and in fact barely even mentions it. As HIV/AIDS is highly correlated with drug use in all the epidemological data I have seen in the west, I don’t think this study allows us to differentiate much of anything.
For example, if you want to determine if lung cancer is predominantly caused by a sexually transmittable virus or toxicological effects of smoking, you need to design studies that carefully differentiate between the two. If you don’t screen for drug use (or smoking) you won’t learn much. Smoking (and drug use) are both highly correlated in long-term couples. If you just simply assume from the get go that the sexually transmitted viral theory is correct, you would naturally see an apparent low rate of transmission proportional to the length of time the couple is together (because this correlates with the smoking behavior ‘catching’.)
So to show that lung cancer is caused by a sexually transmitted vector, you would need to focus on non-smokers. That is why the Padian study is useful, and this African study you point to is not useful.
The part that you seem to think is ingenious—the so called “sequence analysis”, I do not find necessarily ingenious or able to “confirm that transmission was within pairs” in the slightest.
If you want to get into the side discussion on “viral load” and viral DNA comparison based on PCR techniques, it’s critical that you understand Kary Mullis’s objection. Kary Mullis won the nobel for inventing PCR, and he is a strong critic of the whole HIV theory, and the entire interpretation of genetic data based on the technique he invented.
Basically, PCR-like techniques allow you to detect DNA sequences that match a partial fragment, and they allow you to massively amplify those matches—allowing one to find a needle in a haystack by duplicating the needle into a new haystack, so to speak. It’s more useful for qualitative vs quantitative results. The problem with the whole idea of using PCR to test for “HIV DNA” is multi-fold. First, HIV-DNA is allowed to be any of a vast set of sequences—presumably because of it’s massive “mutation” potential. The human body is floating in a sea of RNA and DNA sequences, most of which we know little about—large amounts of various types of RNA that is used to control gene expression, regulatory computation, and regulatory signaling between cells.
So out of that sea of DNA/RNA you get in a tube, a huge set of 10bp-ish sequences are rather arbitrarily determined to be “HIV”, and then one tests many partial sequences and usually finds some similar-ish matches. If you use this PCR test on anybody you will always get some positive results—everybody has some amount of “HIV-ish” genetic material circulating in their blood normally. Comparing sequences in this way is fraught with methodological problems—if you pick some random sequence you will probably find something similar in someone else’s blood, so there is a huge amount of potential sample bias—somewhat like looking for pictures of crystals in ice patterns or looking for coded messages in the bible. There is so many random sequences that it is easy to find some that match, focus on those, and then ignore all the non-matches. A real true similarity comparison would involve a tremendous amount of sequencing on a scale that is—as far as I can tell—never done or not even feasible today. It is not as if PCR gives us some complete snapshot pictureof all the DNA/RNA floating around.
And finally, keep in mind that any way you slice it—we should expect to see sequence similarities in these couples, as they are genetically related—from the same area in africa and much more related on average than two random samples of homo sapiens.
That’s my issue — I don’t think Padian et al.’s zero seroconversions result is sufficiently strong to outright eliminate a possibility, unless one’s already assigned a low prior to that possibility. Personally, I walked into this discussion with a very high prior (something like 99%) for HIV being sexually transmissible to some nontrivial (more than, say, once in every million unsafe sex acts) extent, and the Padian et al. result is not a strong one, so my prior is essentially unchanged.
Since the prior estimates for sexual transmission I’ve seen are already very small (on the order of 0.01% to 0.1%), the Padian et al. result doesn’t really clash with them that much. I also doubt “the most likely cluster” is centred on zero if one accounts for all of the evidence in the study, rather than focusing exclusively on the zero seroconversions result.
It favours a zero transmission rate strongly only if one makes particular strong assumptions about the sexual behaviour of the study’s subjects, and disregards the evidence of risk factors.
Let’s return to one of the papers that kicked off this discussion, as it has a few examples. From page 810: “seroconversions occurred in three male and seven female contacts after enrolment in the study” (that’s not even counting whatever seroconversions had to have occurred in those subjects already HIV+ at the start of the study). There must be some explanation for those seven seroconversions.
Whether or not one believes HIV is sexually transmitted, seroconversions occurred. What were their causes, if not HIV infection due to sexual transmission?
Where does the HIV come from if not an external source?
I’m having difficulty squaring some of your comments on seropositivity and HIV testing with the high reported sensitivity & specificity of properly conducted HIV tests.
I do not see the Madrid study as “largely worthless”, though I’d give it less weight than the Padian et al. study for the reasons you give. (I should emphasize that I’m talking about the Padian et al. study as a whole there; I maintain my reservations about the zero seroconversions result.) Still, the Madrid study sample’s not particularly small compared to the number of Padian et al. couples who consistently had unprotected sex and were followed up prospectively.
Yes. The point I was making was that with the sequence analysis confirming the source of the transmission, the probability of any given seroconverter having been infected by IV drug use with strangers is less than if the researchers hadn’t done the sequence analysis (although of course still more than zero). So, to have me agree that the HIV infections are due to IV drug use, I would have to be convinced that the seroconverters had been sharing needles with their partners. And...
...as the study took place in Uganda, I find it very unlikely that even half of the seroconverters were infected by sharing needles (especially since none of the subjects reported injection drug use). Unless you are now arguing that seroconversion doesn’t actually indicate HIV infection (and I can’t tell whether you are or not), I expect you can see why I’d want alternative explanations for each of these seroconversions.
The African study, I’d say, is weaker evidence than the Padian study. At the same time, I think it’s absurd to write it off as “not useful”. At the risk of repeating myself, my reasoning goes like this: some number of subjects acquired HIV during the Ugandan study; exposure to HIV is necessary for infection; it is not credible to suppose that every HIV exposure that led to seroconversion is attributable to IV drug use. If there were only four or five seroconversions, I’d say it was statistically possible. In fact, the study reports that out of 239 monogamous couples that were initially HIV-discordant, 72 “acquired HIV during follow-up”. The probability that all 72 of these Ugandans acquired HIV by IV drug use is surely astronomically small.
Not especially, to be honest.
I’m not much impressed by Mullis’s Nobel credentials. There are quite a few Nobelists who got the prize and promptly started dabbling in crankery. (Including, as it happens, Luc Montagnier, so this isn’t just an issue for people who downplay the links between HIV & AIDS.) Jim Watson co-discovered DNA’s structure, but I’m not about to take all his proclamations about genetics at face value.
Anyway, I haven’t seen anything in the Uganda study report to suggest they used PCR in so sloppy a way as you’re suggesting, and I doubt they’d have much to report if they had. As such, it’s hard for me to avoid the feeling that your remarks about PCR are something of a fully general counterargument against HIV sequencing.
Right, but two samples of virus from a couple where one member infected the other will nonetheless be far more genetically similar on average than two samples of virus from randomly selected infected people in Rakai.
First off, before we get into anything else, we need to understand and agree on what seropositivity actually means. Seropositivity means a positive result on an antibody test such as western blot, to some combination of antigens identified by Gallo in 1985 in his large scale blood screening tests. He did a large number of tests on transformed (immortalized) cell lines derived from AIDS patients and found a combination of antigens that could screen blood—separating AIDS and pre-AIDS blood from regular blood.
The problem is he (like Motagnier) failed to isolate the ‘virus’, and most or all of the antibodies in the test react or cross-react with antigens to opportunistic microbes (candida namely) and cellular debris. The p24 protein in particular is essentially just a normal cellular wall or microvescile component—so the ‘HIV’ test is really just a general test of opportunistic infection and apoptosis or immune directed killing of CD4 cells (possibly due to widespread viral parasite burden). It is not a measure of ‘HIV’, it is a direct measure of declining CD4 cells and AIDS or pre-AIDS.
more on this
and a longer, more detailed analysis of cross-reactivity for the different ‘HIV’ proteins
The antibody tests are not standardized geographically or temporarily, so it also makes it very difficult to compare across studies—“seropositivity” means different things in different places and times.
As just one random example—most dogs typically have a mix of ‘HIV’ antigens, and are HIV ‘seropositive’ in whole or in part:
from this paper
You post a link to a paper which supposedly shows the ” high reported sensitivity & specificity” of HIV tests. This is not actually what that paper is about, but it references several other papers for this claim—the first I investigated being this. The important quote:
So they are just using Western blot as ‘confirmation’. So they are just using one antibody test to confirm another antibody test—which of course is rather ridiculous.
To actually compute the sensitivity and specificity for a “HIV” test, one needs a gold standard such as viral isolation or perhaps a DNA test. Unfortunately HIV can not be isolated, either because it doesn’t exit or it exists in only minute quantities.
But one can attempt to use the presumed viral DNA as a gold standard, and the result is extremely poor sensitivity and specificity:
Poor sensitivity, specificity, and reproducibility of detection of HIV-1 DNA in serum by polymerase chain reaction. The Transfusion Safety Study Group.
Poor sensitivity is perhaps a gross understatement—the study actually shows that around 18-25% of the population at large test positive for ‘HIV DNA’, and this is only weakly correlated with seropositivity.
You completely dismiss Mullis’s argument based solely on an ad hominem “not much impressed by Mullis’s nobel credentials” without seeming to acknowledge or understand the argument itself.
Seroconversion in the west is closely correlated with AIDS or pre-AIDS. This does not appear to be as true in Africa, so we are generally talking about two different worlds. Part of this may be genetic (black americans have amazingly higher seropositvity in general), the other part may relate simply to higher precedence of opportunistic infections and antigens that seropositivity measures. KS for example is vary rare in the west and along with systemic candidaisis was part of the original AIDS definition, but it is one of the most common cancers in Africa.
I am arguing that.
Seropositivity does not strongly correlate with ‘HIV’ infection (by DNA test), which is why it is better to discuss AIDS itself as being sexually transmittable or not.
The Gallo blood test is tightly correlated with AIDS (at least in the west) - simply because that is what it was designed to do, so you can use that as data for AIDS transmission discussions.
OK. At this point, I’m going to have to disengage and walk away from this debate. I’m realizing that the inferential distance between us is far bigger than I originally thought, and trying to bridge it would need me to considerably ramp up the effort I’m already putting into this. (Even then I can imagine this going on indefinitely, which isn’t a very appealing prospect to me, nor to other Less Wrong posters, by the looks of it.)
I’d still like to respond briefly to one part of your comment, which comments on my own words rather than HIV/AIDS:
It’s wholly legitimate for me to respond to someone citing Mullis’s credentials (as if I didn’t know about them already) by explaining why I give them little weight, and my next paragraph was meant to summarize why I gave “your remarks about PCR” (that is, those you paraphrased from Mullis) short shrift. In other words, I acknowledged the argument by rejecting it.
I’m glad you can walk away, I have a harder time initiating that. I’m curious though about the direction of the inferential distance you see—do you have a biology background?
The dissidents point to a rather surprising pile of evidence that the serological HIV tests are based on rather general, cross-reactive antibodies, and this is essentially a fundamental flaw in HIV science which has never been corrected. Now it may be that the orthodoxy has a really good counter to this, but if they do I have yet to find it. The orthodox position on this, from papers linked to wikipedia, points to studies which measure the sensitivity of various HIV antibody tests by comparing them to . . other HIV antibody tests.
The few large double-blind meta-studies that compare the different antibody tests to PCR tests show terrible sensitivity and specificity between the two, and I haven’t seen the orthodox counter to this. So something is wrong with the antibody tests, the PCR tests, or the whole thing. I imagine it’s a little bit of both—the antibody tests are cross-reactive (hence many dogs test positive), and PCR tests are difficult and subject to experimenter bias.
Perhaps the orthodox counter is that there are a whole big host of HIV related viruses, and the antibody tests are cross-reactive across these related species. This seems to then just beg more questions than it answers, and doesn’t circumvent some of the specific non-viral cross-reactions the dissidents point to.
My paraphrase of Mullis’s argument may actually be a mix of other dissident positions. I just rechecked that part of his book and he covers the difficulty of PCR and the confirmation bias but largely in regards to the OJ trial. On HIV he mainly rehashes Deusberg’s argument.
All right, enough.
None at all. (I expect the inferential distance would be even greater if I did. If I had personal experience of working with retroviruses, for instance, I reckon my prior probabilities for claims like “HIV can not be isolated” or “HIV doesn’t exist” would be far, far less than they are. And they are already very low.)
So those electron microscope pictures are fakes?
Which electron microscope pictures?
When ‘HIV’ was first ‘discovered’ in the original papers by Gallo and Montagnier, they had difficulty isolating and didn’t publish pictures from what I understand—that didn’t happen until years later. Gallo’s great discovery for HTLVIII was based on running a lager number of antigen/antibody tests with an immortalized cell line to find an antibody test that could screen AIDS and pre-AIDS blood from regular blood. That is the basis of all the current HIV tests.
The first published pictures came more than a decade later, and they showed that “HIV isolate” really consists largely of cellular debris and microvesciles. In these EM photos, they do find some occasional particles of roughly the right size and label them as “HIV”, but they could also just be any of a number of other things, and for all intents and purposes, HIV ‘particles’ look like regular microvesciles.
The titles of the papers say it all:
“Cell membrane vesicles are a major contaminant of gradient-enriched human immunodeficiency virus type-1 preparations”
“Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations”
more on HIV ‘pictures’
I have lost the link, but there are better more recent pictures taken with ATM, and they show that for all intents and purposes, it’s impossible to distinguish ‘HIV’ from regular microvesicles that bud from the cell wall naturally. If HIV can be said to exist at all as a unique exogenous virus, it is only because of unique RNA content in the microvesicle, and in this sense is very much unlike all other known viruses.
Of course, the part of HIV’s genome which is supposed to code for the outer envelope is pretty much the same as the endogenous sequences that already exist in the human genome—the HERVs.
Huh. While I still think that the HIV explanation is the most likely one for AIDS, I am slightly less convinced.