As promised, a discussion on the paper, Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study.
First, let’s backtrack a bit and see what’s already been said, lest I repeat myself. The little summary below can also catch anyone up who’s not up to wading through 250-odd comments. Those who’ve already done so can skip the quoted parts and scroll down…
[Note: I've uploaded a .pdf of the Padian paper for anyone to access Here.]
Hank Barnes said here about the paper:
1. It was the longest and largest epidemiological study of heterosexual tranmission of HIV (1986-1996);
2. For 10 years, it followed 175 discordant couples, who had a lotta sex. “Discordant” means for each couple, 1 person was HIV+, and one was not.
3. So, obviously, if you’re gonna have lots of sex with an HIV+ person, you’re gonna get the virus, get AIDS and die, right?
4. After 10 years, the scientists found NO seroconversions.
5. The couples who used condoms, did not transmit the virus
6. The couples who failed to use condoms, did not transmit the virus
7. The couples that exclusively engaged in vaginal intercourse did not transmit the virus;
8. In fact, 39% of the couple engaged in anal sex — they too did not transmit the virus.The only logical, scientific conclusion from the Padian report is that AIDS is not a sexually transmitted disease.
Indeed, How can you have a sexually transmitted disease, that is not transmitted by sex?
If anyone here disputes any of the fact I’ve recited above re Padian, please feel free to read the paper and tell me where I’ve erred.
More importantly, assume my recitation of the paper is true. Then, what logical, scientific conclusion would YOU reach regarding HIV?
Hank is factually correct about some aspects of the Padian paper. No seroconversions occurred during the course of Padian’s study although some may have occurred prior to the study. Over 400 individuals in stable relationships were initially identified as potential participants in this study. When their partners were tested, 15% of the 400 couples were excluded at the outset because the partner was already HIV positive. There was no way to know whether the partners had acquired HIV from each other but neither was there any way to demonstrate that they hadn’t.
However, Hank is wrong about the duration of the study. Individuals were recruited over a ten year period. No couple was actually followed for anything even approaching ten years. 3000 couple months of follow-up for 175 serodiscordant couples – that’s an average of less than two years per couple.
Also there have been other studies of heterosexual transmission of HIV that do show apparent seroconversion in individuals with no known risk factors other than a seropositive spouse. The conclusion of heterosexual transmission is subject of course to all the caveats that apply to studies of human beings.
Enter Darin Brown in the rudely hijacked thread:
Unfortunately, what you say is completely wrong, assuming that the sexual encounters are identically and independently distributed, which would seem to be a fairly reasonable assumption in this case.
Have you heard of random variables? Expected value? The situation you’re describing is something studied in lower-division stats courses — it’s called the geometric distribution. You have a trial with 2 outcomes: success (probability p) and failure (probability q = 1 – p). The geometric distribution assigns to each positive integer n the probability of exactly n trials before success is reached. The situation you describe above is the case p = 1/1000.
Of course “3 seroconversions per hundred couple years doesn’t mean 1 serodiscordant couple can go at it in relative safety for 33 years; or to use your numbers, that an HIV negative individual can have 999 sexual encounters before running into a problem.” That’s not what is being claimed. What’s being claimed is a mathematical statement: that the expected number of sexual encounters before “success” is 1000 = 1/p. And, in fact, that is the case. A random variable with geometric distribution does indeed have mean equal to 1/p.
You are quite wrong with the lottery ticket analogy. It does not matter WHO buys the tickets, what matters is that the trials of buying a ticket to see if you win are identically and independently distributed. And this is true for lottery tickets, regardless of whether one person buys 1,000,000 tickets or 1,000,000 people each buy one ticket. The trials don’t give a hoot about who’s buying the tickets…why should they?
and Dale responds:
Darin, Your post in response to my post on the other hand demonstrates a lack of understanding (or a masterpiece of ignorance if you prefer that term) of biology.
In particular your statement “assuming that the sexual encounters are identically and independently distributed, which would seem to be a fairly reasonable assumption in this case.”
That might be a reasonable assumption to a mathematician but no biologist would ever make such an assumption, particular as applied to human beings.
Human beings are not a homogenous population, neither genetically nor with regard to the environments they live in. Some are more susceptible to HIV infection than others. Sexual encounters are not all the same,some incorporate more risk factors for transmission than others. The viruses themselves also vary genetically and that too will affect transmission rates.
The identification of any individuals in whom sexual transmission of the virus has occured says the virus can be transmitted sexually and a hundred or a thousand population studies such as Padians will not determine the true probability of transmission for any given individual at any given sexual encounter.
Hank Barnes impatiently returns:
1.The year is 1985 — one year after the supposed “cause” of AIDS has been discovered — a virus called HTLV-III (now called HIV).
2. The thought is HIV is sexually transmitted.
3. The thought is once acquired, within 2 years, you die.
4. Most of the folks dying of AIDS are gay males. But, this is a bit nonsensical, since viruses don’t discriminate. They are real dumb and real small.
5. The thought is an infectious disease will likely move into the general population and kill a lot of people.
6. So, a buncha brilliant epidemiologists from San Francisco set out test the hypothesis: Find HIV+ people and observe what happens to their partners when they have a lotta sex. Clean. Easy. Crisp science.
7. So, the a priori hypothesis is this: We expect the uninfected partners of HIV+ people to become infected at some rate. 100%? 50%? Who knows? Padian does not say (for good reason).
8. We get a lotta $$ from the gov’t to fund this study. It lasts 10 years. We test a lotta people for HIV. We follow them for years. They have a lotta sex. We keep re-testing them. So, How many got infected? The answer is:Zero. Zip. Zed. Nada. Nil. Nothing. Nobody.
NOT ONE SINGLE PERSON (175 discordant couples), after unlimited, abundant, (dare I even say wild and kinky?) sexual acts over 10 years contracts HIV. Not one.
Buried in the paper on pg 354 (“We observed no seroconversions after entry into the study”).
Those are the facts. So, what is one to conclude?
My conclusion is that the connection between sex and AIDS has been proven false. Some folks don’t like that conclusion. The ostrich crowd has emotionally invested in the wrong paradigm, and are unwilling to change their beliefs, despite the evidence. Not very scientific, mind you.
Myself, I go with the facts. NO SEROCONVERSIONS. You cannot have a sexually transmitted disease, where sexual activity is abundant, yet sexual transmission is non-existent.
So, put that in your pipe and smoke it!
Some mostly off-topic comments (for the Padian paper analysis anyway), and then Hank asked for this:
Please provide a cite for a 10-year study (or less, if you like) where uninfected folks did in fact become infected from heterosexual transmission of HIV.
Chris Noble enters with this:
OK I’ll bite.
Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda.
The Rakai cohort studies began in 1994.
While the researchers did not have the genitalia of the couples under an electron microscope at the time of transmission they did do sequence analyses to confirm transmission.
Note the strong dependence on the stage of infection upon transmission risk. This confirms earlier studies showing a relationship between viral load and transmission risk. It is also common sense. The risk of transmission of HSV is not constant. It varies with viral load and the amount of viral shedding.
The HIV+ member in Padian’s serodiscordant couples had been infected for a period of time before the start of the study. None were in the initial infection stage.
The HIV dissidents may be surprised that this is exactly what Duesberg has been saying – that the transmission of HIV should be highest during the initial infection stage.
Hank then shifts the goalposts:
Your Ugandan study on heterosexual transmission is interesting, thanks.
But, it seems awful late in the game (published in 2005, regarding results in 1994)
By the mid-1980′s, the scientific community had already declared that HIV was heterosexually transmissible. Padian began her work 10-year study on this topic in 1985. I assert that her results, actually refuted the working-hypothesis.
The question is, What study of heterosexual transmission in the early 1980′s formed the foundation to support the scientific assertion that AIDS was a sexually transmitted disease? Your cite of Rakai is interesting, but dislocated from the historical development of the disease.
Noble “ET AL” — You really must learn to read the body of scientific papers in addition to the abstracts, just like Hank has pointed out (n-times, n > 7). Because if you had read the body, you would know that overall transmission rate in the Rakai study was 1 in 856, over a whopping total of 6700 couple-months. That’s more than TWICE as many couple-months as Padian! They even admit in the discussion, “The overall rate of HIV transmission…is consistent with previous estimates from Rakai, Europe, and North America.” But since this would further confirm HIV can’t possibly cause a sexually transmitted disease, they had to hide this fact a few pages deep into the paper, and let all the lazy eyes glaze over “.0082/coital act within ~2.5 months after seroconversion” in the abstract, a ridiculous statement given the fact it’s only based on 10 couples who were only surveyed ONCE every TEN months…but wait, you would have to actually READ the paper to know that! Silly me.
and JP adds this study:
But this whole debate piqued my interest, and I ended up stumbling across this:
“Incidence of HIV Infection in Stable Sexual Partnerships: A Retrospective Cohort Study of 1802 Couples in Mwanza Region, Tanzania” (Hugonnet et al. 2002 JAIDS 30(1)73-80).
In the text (which I read this time), they show that, of the 42 discordant couples, there are 6 seroconversions in 2 years.
For comparison, there are 1742 couples where both partners are HIV- at the outset. After 2 years, there were 21 seroconversions. The difference between the two groups is significant.
I don’t think you have a strong argument that HIV isn’t sexually transmitted, no matter how you frame it.
A bit more off-topic discussion, followed by JP’s comment:
Darin Brown–
“6 transmissions out of 8400 coital acts is a transmission rate of 1 in 1400. Unless you’re misrepresenting the data.”
Sure. Here’s a comparison:
The transmission rate per sexual act for herpes simplex 2: 1/1200 (from “Effect of Condoms on Reducing the Transmission of Herpes Simplex Virus Type 2 From Men to Women JAMA 2001 285(3100-3106)”)
Herpes is considered to be sexually transmitted. Why not HIV?
[Adding from the conclusion of that paper: "Our study revealed several new findings about the frequency and prevention of transmission of HSV-2 infection to sexual partners. Among monogamous couples with 1 partner who had known symptomatic genital herpes and 1 who was susceptible, we showed that the rate of transmission from men to women is 8.9/10 000 sex acts. This rate is similar to that seen with sexually acquired HIV.--Tara]
followed by me logging on and getting pissed that y’all ruined my happy nephew news with more of this after I already noted I’d come back to it at a later date. Patience, anyone?
So, let me start my portion by summarizing my thoughts on the Padian paper. As others have noted, the paper had 2 parts–a retrospective analysis, and a prospective analysis. The retrospective portion showed findings similar to previous studies–anal sex, history of other STDs, injection drug use, and not using condoms increased the risk of transmission. Nothing too surprising here, and nothing that’s really been harped on by Hank or others. So, let’s get to the meat of the objections.
The prospective portion began in 1990. As noted, 175 couples were enrolled where one person was HIV+ and the other partner negative. However, there were only 282 couple-years of followup, they note that “attrition was severe,” and the longest duration of follow-up was 12 visits (6 years). Additionally, while “3384 couple-months of followup” was observed, note that there were only 2 visits per year. They also say on page 351 that “the couple was counseled together regarding safe sexual practices,” and the stats bear out that many of the couples got the message. Abstention increased from 0% at baseline to 14.5% in the final follow-up visit; consistent condom use increased from 32.3% to 74%, and any anal intercourse decreased from 37.9% to 8.1%. Obviously, these behavioral changes would severely decrease the ability to detect the transmission of *any* sexually-transmitted disease (borne out by the study on herpes cited above).
What’s missing from their paper is data on the distribution of follow-up of the couples. 282 couple-years of follow-up for 175 couples that are only seen every 6 months ain’t a lot. If all of the couples were followed for at least a year, that alone takes up 175 of the couple-years, and only 3 visits per couple (assuming a visit at enrollment, 6-month followup, and 12-month followup). They note that at least one couple made it the whole 6 year period, but it’s not clear from their paper how many couples had significant follow-up (and the risk factors associated with said couples). This also makes their discussion less impressive. As Hank notes, they say that “no transmission occurred among the 25 percent of couples who did not use condoms consistently at their last follow-up nor among the 47 couples who intermittently practiced unsafe sex during the entire duration of follow-up,” but was this duration 6 months? A year? More? How many sexual encounters occurred during this period? Obviously no one reports every single bit of data, but knowing even the average duration of follow-up would be helpful.
Continuing on, as noted in one of the exchanges above, they note they don’t have data on the incidence of the HIV+ partner’s infection–in other words, was the infected partner diagnosed a month before enrollment? A year? Longer? Other studies have shown that HIV is most infectious shortly after acquiring the virus, so that’s another piece of data that would have been nice to have. Additionally, they note in the discussion that there have been a number of host factors identified that have been associated with decreased susceptibility–and none of them were examined in this study. They also noted a low rate of other STI prevalence in the couples included in the retrospective study, but don’t specifically say what this was in the couples involved in the prospective portion. Was it similarly low? Concurrent STI is another risk factor for acquisition of HIV, and if that was essentially absent in the prospectively studied population, that’s another key data element missing.
Next, any study that uses volunteers brings in potential biases, the most obvious one being, “is this group representative of the general population?” Again, they’re lacking stats on a number of things epidemiologists usually look at when grappling with this issue–things like education and socio-economic status (they do provide race and age data). They don’t even mention, however, the total number of couples invited to particpate, or how they recruited couples, though they reference 2 older papers–not available online–and say “study protocol and data collection methods ahve been described in detail previously.” The abstract of one of those says “Participants were recruited from various HIV counseling and testing sites throughout California,” suggesting that they offered enrollment to a cohort of individuals–some accepted, likely many declined. This also brings bias into the study–why did those who declined, do so? Were those who accepted the invitation representative of the group? Why or why not? Again, this may have been addressed in the 1991 paper linked above, but IMO it’s also worth noting briefly in the new paper.
These criticisms may seem like I’m really down on the paper. I’m not, really–overall, it’s not bad, not great. Thing is, I find it rather strange that it’s being used to beat down the idea that HIV is a sexually-transmitted disease. For one, their first analysis clearly shows support for that hypothesis. Two, even the prospective portion of the study wasn’t designed to “catch” sexual transmission in the act. Their introduction notes the reason for the study:
…to address this shift in the epidemic toward heterosexually-acquired infection, a deeper understanding of risk factors for heterosexual transmission is imperative. We have been able to identify risk factors at the individual level that affect the likelihood of transmission between infected individuals and their heterosexual partners. Elimination or modification of these factors could result in reduced transmission of HIV. In addition, predictions about the epidemic might be refined by identification of such risk factors, because their prevalence signifies potential for future epidemic spread.
That’s why their analyses focused on the risk factors for transmission, and how they changed over time–including in the prospective cohort. Indeed, their prospective study design–even without the flaws I note above–is a pretty poor setup for detecting a transmission event. A better–but still far from perfect–design is this study, which collected not only blood but also vaginal swabs, so that the presence of other co-factors could be examined, and the HIV strain could be subtyped. Viral load was also measured, and data was collected regarding stage of infection. That’s data you want when you’re carrying out a study trying to witness transmission events.
Finally, there’s a lot of “this can’t happen” being thrown around by those who don’t accept that HIV causes AIDS. Again, this goes back to my question of why this virus/disease receives special treatment. JP already noted that similar rates of transmission have been found with herpes as are seen with HIV, so you can’t rightly say that HIV “can’t be” a STI without saying the same thing of herpes. (In the study referenced above, they had an even *lower* rate of condom use than the Padian study–so theoretically, with identical levels of condom use, herpes could be even less transmissible than HIV). Duesberg and others note that HIV “discriminates” by race and gender, yet rates of syphilis and gonorrhea are nearly 30 times higher in blacks than in whites. Do these also not cause the diseases they’ve long been associated with? Similarly with male-to-female ratios of the disease: we’ve seen the same thing during outbreaks of hepatitis A and shigella, among others. As I said before, this can easily be explained as a type of founder effect due to the original group HIV was introduced into in the US. The rest of the arguments are just more of the same–retroviruses “can’t” kill cells, or HIV “can’t” cause disease after antibodies are present (what about shingles?), or is too small or “simple”–it “can’t” cause AIDS (what about rabies, West Nile, polio, HPV, influenza–all with genomes of similar size? Or teeny-tiny Hepatitis B at only 3000 bp, going around and causing all that cancer? [Of course, Drs. Bialy and Duesberg don't think viruses cause cancer, either]). You get the point.
Last but not least, even though I may be young (though I’m not exactly a “recently minted” PhD–I finished grad school in 2002), even I’m not naive enough to say some microbe “can’t” do something–others have done it, and been proven wrong. If anything, studying all sorts of microbial life over the past decade-plus has made me aware of all the crazy things microbes can do. Hell, that’s one reason I started this site–there’s a never-ending stream of fascinating new discoveries in the microbial world to discuss. And this will further piss some people off, but again, I see a parallel here between creationists and many of y’all who rail against HIV. We don’t have all the answers yet, therefore, hey, let’s just throw in the towel. One of the oddest objections to me is that we don’t have a vaccine yet, “despite 20 years of searching.” Again, I’ll note that we don’t have vaccines against group A or B streptococci, even though group A has been studied for well over 100 years, and group B for 30 years now. Nor do we have vaccines for other pathogens that emerged ’round the same time as HIV, such as E. coli O157:H7. Like I said–special treatment. Mystifying.
Anyhoo, apologies for this being a bit long and rambly–I’m trying to get some answers to objections in that I think fit in with the Padian paper analysis. I’ve not overlooked other questions waiting for me, and have some other posts in the hopper, but I’d prefer to try to keep this a bit more focused. I think the material above provides a lot of fertile ground for discussion, but I’ll note a few things: 1) I ain’t at your beckoned call–I have a life, a family, and a grant due Tuesday, so if I can’t answer your right away, them’s the breaks; and 2) must you resort to name-calling? “Dumbass”? “Weenie?” If you’re going to fling insults, dear lord, at least do it at a junior high level. Graduate to “vagina blood fart” or something.
Okay, have at it.