Tenofovir fail

Posted by ERV on November 29, 2011
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One problem we have to deal with in HIV-1 world (of the many problems we have to deal with) is that no one is ‘cured’ of HIV/AIDS (except this guy).

So people who are infected go on to infect more people, who go on to infect more people, who go on to infect more people… I mean thats how we *got* a pandemic.

So since we cant get rid of HIV-1 once it has infected someone, it means the trick to stopping the pandemic is to stop new infections. Interrupt the dominoes falling, protect the down-stream dominoes.

We have a way of doing that: condoms.

But for any number of reasons, condoms are not always used, so transmissions continue.

So thats why I am working on an HIV-1 vaccine. You might not wear a condom all the time (by choice, or by situation), but your antibodies and CTLs will still be there to protect you if youve gotten an anti-HIV vaccine.

… In case you havent noticed, we are having some difficulty making an efficacious HIV-1 vaccine… *blink*

So other people are exploring other ways to prevent new HIV-1 infections. One idea– using the anti-HIV drug tenofovir as a once-daily medication or as a component in microbicide to prevent new HIV infections (analogous to The Pill and spermicides for preventing pregnancy). Initial studies looked promising!

… But in a larger group of heterosexual women (over 5,000) in Africa, tenofovir hasnt worked at all. The Pill arm was pulled earlier this year, and the microbicide arm was pulled last week:

* 6.1% in the inactive placebo gel group acquired HIV in a twelve-month period
* 6% in the tenofovir gel group acquired HIV in a twelve-month period

The best we can hope to get out of this, is to figure out why tenfovir did not work in either form in this study, and hopefully we can figure out how to fix it.

Dammit.

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Comments

  1. #1 Mu
    November 29, 2011

    6% annual uptake gives you a 70% infection rate after 20 years. That’s horrible.

  2. #2 Justicar
    November 29, 2011

    Boy am I glad I put on a condom just to read that then.

  3. #3 EvilYeti
    November 29, 2011

    That’s a terrible idea.

    There is already evidence that this sort of pro-active daily treatment, even if its a placebo, will actually encourage risky behavior. So folks end up skipping that condom now and then because they are on medication.

  4. #4 Paul
    November 29, 2011

    Damn!

    I think that you probably hit on the reason these failed in an earlier post when you wrote:

    “People who took the drug as instructed, had a 92% lower chance of becoming infected than placebo.

    YAY!

    … Yeah, no, read that again: “People who took the drug as instructed”.

    Lots of people didnt take the drug properly, which is just asking for trouble, evolutionarily, and was a problem practically in that the overall lowered risk in the treatment group was only 44%, not 92%.
    ”

    Condoms are not a perfect barrier against HIV infection, but I suppose the great advantage that condoms have over these methods is that it is a lot easier to use them correctly, and, perhaps more importantly, to tell when they are not being used correctly.

  5. #5 R2
    November 29, 2011

    It might encourage risky behavior, but for people in either serodiscordant couples or who are in a high risk group something like this that works might help them have another way to protect themselves. It’s like saying the birth control shouldn’t exist because women will become more “promiscuous”.

  6. #6 mary
    November 30, 2011

    yup…dammit effing virus always finds a way!

  7. #7 windy
    November 30, 2011

    It’s like saying the birth control shouldn’t exist because women will become more “promiscuous”.

    It’s not quite the same thing, if the risky behavior actually has the potential to negate the gains from the medicine. If women on birth control were ending up pregnant as often as those without, we’d have to be concerned about their risky behavior, as well.

    Someone gets nicely pwned in the comments of that tenofovir gel article, by the way. Also, if this person is so concerned about the poor, illiterate women that are recruited to these trials, how is pimping her BOOK supposed to help?

  8. #8 daedalus2u
    November 30, 2011

    Everyone knows that a microbicide is not going to be as good as a condom, but many women are unable to compel their partner to use a condom because he will beat the crap out of her.

    The Catholic Church opposes the use of condoms (except for gay people) because condoms are a form of birth control.

    What we should do is everything that reduces the transmission of HIV simultaneously. Unfortunately many people don’t care about HIV transmission, so long as it is transmitted to someone they hate.

    It is a lot easier to blame the victims, especially if they are someone you hate (i.e. gays, people in Africa, unmarried people having sex, sex workers) than to do something effective to reduce transmission.

    Anyone who has read about the hoops that have to be gone through to do these trials would appreciate how difficult they are and how much care is being taken to ensure the participants are not exploited. These are extremely difficult trials to do.

    It is trivially easy to pick at them and find supposed flaws. The other comment at the link says that no one should get placebo. Hello? They don’t know if the gel is effective or not, so they don’t know if the active gel is just a placebo itself. That is what the trial is supposed to measure, and what it measured was that the active gel is no more effective than a placebo.

    The goal of microbicides is to do something to slow the rate of infection while people like ERV generate a vaccine that will cure/prevent HIV. We should be doing everything that we can do to slow the progression.

  9. #9 windy
    November 30, 2011

    the book-pushing has now been edited away from the comments at Medical News Today, in case anyone is wondering what the heck I was complaining about.

  10. #10 EvilYeti
    November 30, 2011

    HIV/Aids is almost entirely a lifestyle illness at this point.

    Meaning simply that the best preventive method is avoiding certain high-risk behaviors. In fact, I’ll even suggest that pre-medicating those that engage in high-risk behavior will ultimately create new resistant strains of the virus.

    This is bad idea for the same reason “preemptive” use of antibiotics is a bad idea (except for very specific use cases).

    Re: Contraceptive pills.

    This is a form of birth, not disease control. And I’m STDs are up as a side effect of their use, but don’t ask me for a cite.

    Re: an AIDS vaccine. With apologies to Abbie, I don’t think its possible. Would love to be proven wrong, though.

  11. #11 Dave
    November 30, 2011

    HIV/Aids is almost entirely a lifestyle illness at this point.

    As long as “being a woman in South Africa” counts as a lifestyle.

  12. #12 daedalus2u
    November 30, 2011

    Dave, you mean being a woman in southern Africa or sub Saharan Africa.

    EvilYeti, the issue is not the same as “preemptive” use of antibiotics.

  13. #13 EvilYeti
    November 30, 2011

    Dave,

    I could go into some of the sexual “habits” that African women voluntarily engage in, but I wouldn’t want to put you off your dinner.

  14. #14 Daniel
    November 30, 2011

    Hi Abbie,

    Did you see this? Is there anything in it?
    http://www.nature.com/news/gene-therapy-can-protect-against-hiv-1.9516

    Daniel

  15. #15 R2
    December 1, 2011

    “Almost entirely lifestyle choices”? I can agree that certain behaviors are mostly to blame for the spread in higher income countries… but it’s not a slut disease.

    @7. I was mostly saying that women using hormonal birth control might be more likely to get STDs. But my bigger point was: If I don’t engage in risky behavior but want to take extra steps to take care of myself, and therefore (hypothetically) it would reduce MY risk, should I not be allowed to use it because others might misuse it? Could the risky behavior just be reduced with patient education and in the long run it would be a gain?

  16. #16 harold
    December 1, 2011

    Evil Yeti –

    That’s a terrible idea.

    There is already evidence that this sort of pro-active daily treatment, even if its a placebo, will actually encourage risky behavior. So folks end up skipping that condom now and then because they are on medication.

    The data presented here do not support that conclusion.

    If behaviors were the same with or without the tenofovir, but the tenofovir didn’t work, we would expect to see similar rates of infection in both groups. Which is what we do see.

    If the presence of tenofovir reduced condom use, relative to controls, we might see similar rates of infection (if some beneficial impact of tenofovir exactly balanced the negative impact of changed behavior), or we might see lower infection rate (if tenofovir worked well enough to offset the impact of negative behavioral changes), or higher rate of infection in the tenofovir group (if tenofovir didn’t work, or didn’t work very well, but behavior changed in a negative way).

    Given that rates are the same, behavior changes can’t be ruled out, but the more parsimonious interpretation is that tenofovir didn’t work.

    Re: an AIDS vaccine. With apologies to Abbie, I don’t think its possible.

    I suspect that you lack sufficient background qualifications to make meaningful predictions in this arena.

    Your “apologies” come across as insincere, and this comment comes dangerously close to looking like offensive wishful thinking.

    HIV/Aids is almost entirely a lifestyle illness at this point.

    This statement is absurd. HIV/AIDS is a viral illness; certain behaviors (sometimes including vaginal intercourse between men and women) are the risk factors for contracting it. In the absence of the virus, no “lifestyle” can cause it, so that claim that it is “almost entirely a lifestyle illness” is nonsensical.

    It is true, and a very good thing, that behavioral modification, such as the use of condoms and compliance with medication if infected, can massively reduce the risk of transmission.

    That is not a rational argument against supplementing these approaches with other approaches.

  17. #17 autiemum
    December 1, 2011

    @13 EvilYeti wrote: “I could go into some of the sexual “habits” that African women voluntarily engage in, but I wouldn’t want to put you off your dinner.”

    Please tell us.

    I was under the impression that African women had very little choice about the sexual “habits” they engaged in because they were offered very little choice by the men in their lives.

    Perhaps you are referring to the babies who voluntarily engage in sexual intercourse with HIV-positive men in order to cure them? They are very naughty babies I agree and deserve everything their lifestyle choices bring them.

  18. #18 EvilYeti
    December 1, 2011

    The stupid, it burns.

    Anyway, prophylactic use of internal antivirals or antibiotics except under very controlled conditions (to prevent misuse/abuse) is an undeniably bad idea.

    External use I’m more open too. Especially if it was engineered directly into packaged condoms. Defense in depth is always a winning strategy.

    Googling around shows there are some reluctance to condom use due to cultural or religious issues; which is again a lifestyle thing.

    autiemum,

    I’m specifically referring to “dry sex”

    http://en.wikipedia.org/wiki/Dry_sex

    The baby-rape thing you are referring to is due to a misguided belief (dating back to the middle-ages) that sex with a virgin will cure venereal disease. Again, this is cultural (aka lifestyle) phenomenon of which AIDS is only a symptom.

    My point is that Africa is a pretty fucking backwards hell-hole of a country in many places and if you aren’t killed by AIDS, malaria or ebola then all you have to worry about are the various ongoing civil wars and genocide. I work with a few folks from Nigeria and none of them are homesick.

  19. #19 EvilYeti
    December 1, 2011

    Harold,

    I consulted on the first distributed HIV bioinformatics program over a decade ago, the “Fight AIDS @home” project.

    see: http://fightaidsathome.scripps.edu/

    Based on my limited understanding of the structure and mechanism of HIV infection, it was my opinion at the time that a vaccine would be unlikely. So far I’ve been right and as mentioned would very much love to be wrong.

    Which is irrelevant, I think, due to the recent advances in gene therapy. Which include one confirmed case of a cure under very specific circumstances.

  20. #20 windy
    December 2, 2011

    I would hope that a discussion of the HIV epidemic on ERV could aspire to something a bit better than over-generalizations like ‘Africa is a backwards hellhole’ (not a “country” as I’m sure you are aware) or, for that matter ‘African women have very little choice about their sex lives’. Nigeria, in fact, has a relatively low prevalence of HIV. The countries that have the highest prevalences of HIV at the moment include some of the least hell-holey on the continent.

  21. #21 EvilYeti
    December 2, 2011

    South Africa is a country! And I very clearly stated “parts” of Africa are hellish, which I don’t think anyone is going to deny. Other parts are very nice, actually.

    The point I’m trying to get across is that “AIDS in Africa” is as much a cultural phenomenon as anything.

  22. #22 Justicar
    December 2, 2011

    Based on my limited understanding of the structure and mechanism of HIV infection, it was my opinion at the time that a vaccine would be unlikely. So far I’ve been right and as mentioned would very much love to be wrong.

    EvilYeti, I can do you one better: based on my complete ignorance of the mechanisms by which HIV infection occurs, I predict the next 25 vaccine trials will fail. Oh, that’s because I’m also taking into account that all* lines of treatment have so far failed thereby concluding it’s extremely difficult to pull off and will likely not happen so few trials.
    Wish I were wrong.

    Well, except that one cancer and hiv patient who had the marrow transplant. But that one’s a one off – quite literally.

  23. #23 windy
    December 2, 2011

    @21: ok, but you did say Africa, not South Africa… (where I work at the moment so obviously I don’t find it completely hellish)

    The point I’m trying to get across is that “AIDS in Africa” is as much a cultural phenomenon as anything.

    Well, if we’re trying to find out how culture contributes to the epidemic, we should probably try to narrow it down a bit more… “dry sex” is one such factor, but I don’t think it’s limited to the hardest hit areas.

  24. #24 EvilYeti
    December 4, 2011

    Justicar,
    HIV is a big, complicated virus. This makes it both (relatively) difficult to contract and (relatively) difficult to develop a vaccine for.

    I already mentioned the ‘one off’ cure, which was just a very heavy-handed form of gene therapy. But it absolutely was not a ‘vaccination’ in any sense. The doctors literally deleted the patients immune system and installed a new one from someone with a natural HIV immunity.

  25. #25 Benoni
    December 5, 2011

    Hey EvilYeti. I live in this little bit of Africa:

    Its rather pleasant. So go “dry sex” yourself.

  26. #26 EvilYeti
    December 5, 2011

    Fail.

    “Crime is a prominent issue in South Africa. South Africa has a high rate of murders, assaults, rapes, and other crimes compared to most countries. Many emigrants from South Africa state that crime was a big factor in their decision to leave.”

    http://en.wikipedia.org/wiki/Crime_in_South_Africa

  27. #27 EvilYeti
    December 6, 2011

    re: the whole lifestyle thing…

    http://www.avert.org/usa-transmission-gender.htm

    And I’m not judgmental. I’m simply pointing out that certain behaviors are high-risk when discussing HIV transmission.

  28. #28 Benoni
    December 6, 2011

    Does having unprotected sex (hetero or homosexual) count as a “lifestyle thing”? If yes, your claim is trivial. If not, your claim is false. Congrats!

    As for “Many emigrants from South Africa state that crime was a big factor in their decision to leave”: Many emigrants from SA are racist douchenozzles that think that white Afrikaners are victims of a secret government sanctioned genocide. The opinions of emigrants is irrelevant. As for the actual stats: sure crime is a prominent issue. So what? Its still a fantastic place to live. Try visiting us before declaring “Africa is a pretty fucking backwards hell-hole of a country”.