PrEP makes no sense for discordant couples – corrected

First PReP worked for gay men, and we were happy. Then it didn’t work for straight women, and we were sad. Now, two big studies in heterosexuals have shown it can work for straight couples, and we are deeply confused. Or at least I am.

Taking anti-HIV pills every day cuts the risk of infection by 63%, said CDC researchers in Botswana. It cuts infection by up to 73%, said University of Washington researchers working in Kenya and Uganda. That’s great news, of course.

Here’s why I’m confused. The larger of these trials was conducted in 4,758 “discordant couples”. [I earlier incorrectly reported that both trials were in discordant couples. The CDC trial in fact recruited 1,200 sexually active uninfected heterosexuals, regardless of their partner status. Full inclusion and exclusion criteria here]. That means researchers in the large discordant couple trial knew that one person was infected and the other uninfected. They chose to give drugs to the uninfected person, to see if it would stop them becoming infected. And it does, in over 60% of cases. But another recent study shows that if we give the drugs to the infected partner, the one who might actually need these same drugs because they have HIV and need it surpressed, it cuts infection by 96%. So in the case of discordant couples, it seems to make much more sense to give the antiretrovirals in question to the infected partner.

That leaves us with the question: who should get PReP? Right now, there are not enough antiretrovirals to go around to treat all the sick people who need treatment. If we’re going to use them selectively for prevention, we should start with the most effective use, which appears to be early treatment of the infected partner in discordant couples. We could also give them to people who aren’t in a couple but who know that they’re likely to get around a bit and might want to stay safe without using condoms. That’s potentially a lot of people; it will stretch our purses. But more than that, it will stretch our political will. Let’s face it, HIV has reached eye-watering levels in many sub-Saharan African countries because both voters and governments have been in deep denial about their own, and their neighbours’, propensity to have sex with someone who is not their single life-time partner. Some people, including influential religious and community leaders, even continue to believe that giving out condoms encourages licentious sex. To them, giving out ARVs will surely mean encouraging licentious unprotected sex (if you’re anti-condom, is that better or worse?).

So who is PReP for? We’ve got a better option for discordant couples. We’re not going to want to give it to randy adolescents. We know it works for gay men, but some of the countries where the trials took place would rather thump or jail gay men than protect their sexual health. We’ve no idea yet if it works for drug users (though a deeply unethical trial by CDC in Thailand will tell us that soon.

Of course PReP will find its niche; when people actually take it it works really well (though not as well as abstinence, when people actually abstain, or condoms, when people actually use condoms). We’ll find out a bit more about just how well at the annual AIDS circus in Rome next week. I’ll look forward to learning what the actual incidence rates in the studies were, and more about sex differentials and adherence. But I think we would be unwise to rush around talking about massive roll-out of PReP before we actually figure out who it works for in the real world.

As an aside, the results have a huge potential impact for Gilead, manufacturer of both Viread (bascially tenofovir, one of the pills that worked in the trial) and Truvada (the tenofovir – emtricitabine combination that was the other). Gilead has come over all generous and has started letting Indian and other developing country companies copy their products. They’ll take a 5% fee; if we really do go for a massive roll-out of PrEP, that will keep drug costs down globally, while giving Gilead extra cash for very little effort. A win-win situation for which they should be congratulated.

A second aside: The CDC trial is confusing in a different way. In December 2009, CDC announced it was terminating the trial of Tenofovir for HIV prevention because they’d had so many drop-outs that the trial would be unlikely to show results even if they doubled the size of it. They kept it going not as an efficacy trial (testing Tenofovir against a placebo) but as a safety and behavioural trial (clocking how good people were at taking their pills, looking for side effects etc.). So it was quite surprising to find them leaping forward with efficacy reults, of which more details here.

Thanks to Eva for pointing out my error.

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This post was published on 15/07/11 in Science.

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  1. Comment by Gwinyai Masukume, 16/07/11, 03:22:

    “Let’s face it, HIV has reached eye-watering levels in many sub-Saharan African countries because both voters and governments have been in deep denial about their own, and their neighbours’, propensity to have sex with someone who is not their single life-time partner.”
    As always, I congratulate Dr Pisani for her erudite and thought provoking analysis of PrEP studies. I would like to challenge the above quoted statement:
    HIV is known to be a disease of poverty along with TB, malaria, maternal mortality and so on. In Zimbabwe (which is a sub-Saharan African country) for example, it is widely known by voters and the government that people have a ‘propensity to have sex with someone who is not their single life-time partner’. The social phenomenon of ’small houses’ (extramarital heterosexual sexual intercourse) is commonly parodied in the media and during social interactions. I specifically mention extramarital heterosexual sexual intercourse because HIV largely has a heterosexual face in sub-Saharan Africa. Behavior change, for example, the reduction in the number of multiple concurrent sexual partners has been identified as one of the reasons for the declining HIV prevalence in Zimbabwe.
    In conclusion, denial exists in sub-Saharan Africa but is it very different from the denial that exists elsewhere?

  2. Comment by Jon Jay, 19/07/11, 05:25:

    I agree that in general, treating the HIV-positive partner will be a better use of ART than PrEP in the HIV-negative partner. But the new study results will be useful for discordant couples in which the positive partner is not willing to start ART (or even be tested in the first place). People often face HIV risk because their male partners won’t use condoms–and we can imagine that male partners who won’t use condoms would often be similarly unwilling to be tested for HIV or begin ART before it’s necessary for their own health. PrEP (like microbicides) could be used without a partner’s knowledge or consent. So I think the new PrEP data are potentially useful for discordant couples, despite the efficacy of the 052 regimen.

    I think another interesting question (especially given what you’ve said about the CDC study in Thailand among IV drug users) is the ethics of these studies’ having continued after the HPTN 052 results were released. At that point, there was a known effective intervention (early ARV treatment of the HIV+ partner) which was not being provided to study participants–instead, study participants continued on either to placebo or PrEP (which later failed to show effectiveness among women in FEM-PrEP). So there were probably some preventable infections, especially in the larger Partners study. On the other hand, immediate therapy in discordant couples is still not a worldwide standard of care. Any thoughts? This may seem moot because the studies were just about to finish, but the larger Partners study was slated to continue longer before being stopped by the DSMB.

  3. Comment by Eva, 23/07/11, 07:58:

    I can´t find where the Botswana study says the trial participants were in serodiscordant relationships, do you have a link?

  4. Comment by Roger, 31/07/11, 11:08:

    The use of PrEP in serodiscordant couple when treatment is more efficacious did puzzle me too. However, after a number of discussions a twofold rational started to emmerge:

    (a) the HIV-neg does not know if his/her HIV+ partner is taking his drugs properly to the extent that (s)he is not infectious and (b) that same HIV-neg partner may be having some fun with someone else than her/his regular, HIV+ partner on ART.

    Regarding (b) my response is that the “third party” may not neccessarily be HIV+, and even so, if (s)he was on treatment too that would limit the extent of the problem.

    Regarding point (a), I think it illustrates a potential weekness of T4P.

    But what this discussion is really ignoring, is that the problem is not about who should be treated, but about (un)safe sex. Once more, people are talking pass each other and resolve to medical interventions rather than addressing the root cause of the problem.

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