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jacob_cannell comments on Open Thread, September, 2010-- part 2 - Less Wrong
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If I can take the liberty of butting in...
Here's the table of data I believe you're referring to:
It cites references 76, 77 & 79, all of which turn out to be publicly available online. That's good, because now I can check the validity of Perplexed's claim that the studies backing your CDC data used samples of relatively healthy, well-off people who lack some risk factors.
I took ref. 76 first. It reports data from the "European Study Group on Heterosexual Transmission of HIV", which recruited 563 HIV+ people, and their opposite-sex partners, from clinics and other health centres in 9 European countries. (Potential sampling bias no. 1: HIV+ people in European countries are more likely to have access to adequate healthcare than many Africans and Americans.) It also says:
That fits Perplexed's claim that the study's couples were "regularly examined by physicians" and "instructed in the use of condoms to prevent transmission". It's not clear whether they were "monogamous", but the study did exclude "[c]ontacts reporting other risks of HIV infection and those with other heterosexual partners with major risks for HIV infection". I also see another sampling bias: if the man & the woman in a couple disagreed on their questionnaires, that couple was blocked from the study. I would think that such couples have a higher risk of transmitting HIV (as I'd guess they're more likely to be couples where someone's lying about their sexual history); if so, the study's more likely to lowball HIV transmission risks.
What about refs. 77 & 79? Where did their data came from? It's pretty clear that they used the same European Study Group data. From 77:
And 79:
To be explicit: the three studies you're citing (via the CDC) are based on one data set, and Perplexed's characterization of that data is essentially accurate. That adds credence to his claim that the transmission rates you're citing don't represent HIV transmission rates in other situations.
Incidentally, tables 2 & 3 of ref. 76 suggest that HIV transmission risk is not only associated with type of sex act, but also with the HIV+ partner's infection stage, especially (I did not expect this!) for male partners of HIV+ women. Maybe more evidence that there's more to HIV transmission risk than who's putting which organ in which orifice?
By all means. While you were writing this I was reading 76 and writing my own reply.
Ah I hope he wasn't claiming this, because they certainly were anything but healthy, with around 20% being hardcore IV drug users, 23% transfusion recipients, 10% hemophiliacs, and overall high rates of STD's.
I noticed the discrepancy about sexual history part but I didn't see how to factor it. They are relying on self-reporting to make any of these links.
Err, no, because his characterization is based on the idea that these couples were using condoms frequently, but the study specifically shows that is not the case - see my reply to Perplexed.
If you want to characterize this study, fine, but don't pretend that these are "regular couples regularly using condoms" - that is not what the study claims.
And finally this is the orthodox data. I mean if you want to reject ... ok .. and then we move to searching for other data which supports our relative positions . . . to the extent we have positions.
Perhaps it would be best to agree what the ideal study would be and precommit to that ideal in a sense? And then we could look for other studies that may be closer. Of course in the real world they will rarely be clear cut.
I quite agree that they weren't healthy in absolute terms; I just meant that they were relatively healthy for people with HIV. Compared to HIV+ people in much of the rest of the world, especially sub-Saharan Africa, I'd expect this European study's subjects to have (on average) better nourishment, better healthcare, stronger immune systems, less exposure to infectious disease, much less exposure to parasites, and a far lower rate of promiscuity & prostitution. I should've been more explicit that that was the sort of comparison I had in mind.
Looking at your reply, I think we disagree about whether or not Perplexed was hinting that the couples were consistently using condoms. I didn't think Perplexed was implying anything more than that most cases of HIV transmission involve people who weren't regularly reminded to use condoms. So I took his statement at face value, in which case it's surely true (unless European doctors have come up with a way of counselling couples "about the risk of HIV infection and safer sex practices" that doesn't involve advising condom use!).
I don't believe Perplexed or I are pretending that these are normal couples who continually use condoms. I think it goes without saying that these weren't "regular couples" — after all, "regular couples" don't visit hospitals and clinics to get HIV infections checked out. Whom are you quoting?
I reject your interpretation of the data, rather than the data. The study probably gives a fair idea of transmission risks among faithful Western couples living in the 1980s/90s who regularly see doctors...but for that reason (among others) it's likely to underestimate transmission risks in other demographics.
I think you're probably right on that point. I suspect that looking at per-sex act transmission risks isn't going to be very enlightening about whether or not HIV causes AIDS. It would be better to have data from
(each bullet point getting more restrictive). I don't know if there are such data, but it would get us closer to the original question than big-picture arguments about transmission risks.
I generally agree with most of this except perhaps the last part - I doubt that promiscuity and prostitution varies that much from 3rd and 1st world.
I think he was implying that the reminders led to condom use, but this was in fact not the case according to the study itself (possibly because they excluded many of the condom users, some aspects of the study's design are not all that clear to me).
Not quoting, just paraphrasing. He was implying that the heterosexual couples receiving counseling were not indicative of a typical HIV hetero population, but the study designers of course realized that and were at least attempting to gather representative data.
Ok, whether HIV causes AIDS is a larger topic. My original point was just about the orthodox claim that HIV is sexually transmitted, which I believe is rather obviously bogus according to the orthodox's own data. I hope you can see how the orthodox could go wrong there and some of the political factors at work.
As to the larger HIV == AIDS issue, I largely agree with your ideal data criteria, but one potential issue is whether we are comparing HIV to the null hypothesis or to some other hypothesis. I don't think any reasonable skeptic claims that HIV is not at least correlated with AIDS - Richard Gallo may be many things, but he is probably not stupid nor a charlatan.
So it would be better to compare the orthodox HIV hypothesis vs the Drug/Lifestyle Hypothesis (which predated HIV). Some immediate concerns are that one must take care to then define AIDS reasonably without circular reference to HIV (which precludes some data)
The next concern would be that either way, previously healthy people don't get HIV or AIDS, in reality or according to either theory. The risk groups are all unhealthy in various ways.
All that being said, Duesberg does indeed provide data very close to what you are proposing. There are some groups of HIV+ who, for whatever reason, have refused mainstream treatment. There aren't many such people, but he cites a study about a group in Germany - they are called long term non-progressors (which is kind of funny when you think about it - AIDS is progress?).
Anyway, this study is small, only 30-40 people IIRMC, but it is long lasting and only a handful have died. He calculates their death rate as measurably lower than the death rate of HIV+ treated patients, and uses this as a major piece of evidence.
here .. that part is on page 402 (it's a large journal excerpt or something - not really that long)
An interesting read overall, would like to read a good rebuttal.
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.
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.