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satt comments on Open Thread, September, 2010-- part 2 - Less Wrong
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Quite possibly, but note that I was comparing the subjects in the European study with the rest of the world, rather than all of the 1st world. The study's screening procedures probably cut out quite a few people who have a lot of sex.
I think I do. (I hope I do!) Still, I do see the orthodox belief that HIV can be transmitted sexually as being compatible with the CDC numbers. The CDC transmission rates are surely below the average real-world HIV transmission rate (due to the nature of the European study sample), 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".
It might even preclude the Duesberg/Koehnlein data you link. Page 402 says the study's of "AIDS patients", and it's not clear from the immediate context what definition of "AIDS" was used for the study. All 36 of the patients (you were right about the study's size!) are listed as being HIV+, which suggests to me that the AIDS diagnoses were made (at least partly) based on HIV+ status, as is standard practice.
I would have thought that healthy people are capable of getting HIV? Getting pricked with an HIV-infected needle works, as does sexual transmission. A lot of people in high-risk groups are unhealthy, of course, but there are surely unlucky people who get HIV without prior major illness.
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.
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?)
I should say upfront that there's no way I'm rebutting all 30 pages of the article (I really doubt the game's worth the candle), but I can comment a bit more on the little German study.
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? 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. 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).
I'm also not sure that some of these "AIDS patients" had AIDS in the first place. This looks like the CDC's definition of AIDS: typically, you have to HIV, and either a CD4 count below 200 ("or a CD4+ T-cell percentage of total lymphocytes of less than 15%") or one of a list of AIDS-defining illnesses. (You might dispute using HIV+ status as part of the definition of AIDS, but it makes no difference with Koehnlein's subjects because they all had HIV.) The table doesn't offer enough information about CD4 T-cell percentages to check whether they're less than 15%, but it does give CD4 counts and list what appear to be the patients' "initial AIDS-indicator symptoms".
So I look at case 1. His CD4 count is 256. His initial symptom was "Herpes zoster". The Wikipedia/CDC list of AIDS-defining diseases does not include herpes zoster, only chronic ulcers due to herpes simplex. It's not clear that the patient actually had AIDS when Koehnlein included him in the study. Moving on to case 2, she's marked as asymptomatic and no CD4 count is given. What was the basis for her AIDS diagnosis?
I sorted the 36 cases into 3 groups: a "questionable diagnosis" group (patient was asymptomatic/had symptoms clearly not on the AIDS-defining illness list, and their CD4 count was explicitly given as >200), a "definite AIDS" group (patient had an illness clearly on the AIDS-defining list, and/or a CD4 count explicitly <200), and an "unsure" group (cases that didn't fit the other two groups). I put cases 1, 8, 9, 17, 19, 20, 23, 24, 25, 27 & 35 in the "questionable" group; cases 3, 4, 6, 12, 13, 21, 30, 31, 32 & 36 in the "definite AIDS" group; and cases 2, 5, 7, 10, 11, 14 (they had pneumonia, but only recurrent pneumonia and/or PJP is AIDS-defining), 15, 16 (they had toxoplasmosis, but it's not said whether it was in the brain), 18, 22, 26, 28, 29, 33 & 34 in the "unsure" group.
So the Koehnlein's study's effective sample size & death rate seems to be sensitive to how rigorously one defines AIDS. As I see it, only 10 of the 36 cases unambiguously have AIDS, and counting deaths in that subgroup leads to a death rate of 20% as opposed to "only 8%". I think Koehnlein's data are interesting, but there are a multitude of reasons not to take Duesberg's 8% vs. 63% comparison at face value.
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:
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.