July 13th, 2011

More Favorable Results on PrEP, But …

As part of the usual flurry of studies released just before major scientific meetings, results of two pre-exposure prophylaxis (PrEP) trials in heterosexual men and women have just been made public:

  • In the CDC TDF2 study, 1200 HIV-uninfected men and women in Botswana were randomized to take oral tenofovir/FTC or placebo daily. Tenofovir/FTC was found to reduce the risk for HIV acquisition by 63%. The risk reduction was even greater (78%) among individuals believed to be taking the study drugs.
  • In the Partners PrEP Study, the uninfected partners in nearly 5000 HIV-serodiscordant couples in Kenya and Uganda were randomized to take oral tenofovir/FTC, oral tenofovir alone, or oral placebo daily. Relative to placebo, tenofovir/FTC was associated with a 73% reduction in risk for HIV acquisition, and tenofovir alone was associated with a 62% reduction in risk. The protective effects were similar for both men and women.

So, the score so far on PrEP studies: four positive (if you include CAPRISA 004, which used tenofovir vaginal gel, and of course iPrEX) and one negative (FEM-PREP, in women). Other key (if unsurprising) findings are that PrEP works better if you take it and that it’s pretty safe.

One possible interpretation of these results is that we should do everything we can to get HIV-negative individuals from serodiscordant couples on PrEP as soon as possible.

But here’s another thought: Why not get all the infected people — especially in established serodiscordant couples, as in Partners PrEP — on ART? According to Study 052 (with many more details to come next week at IAS), the net result of this strategy would be both a personal and a public health benefit. Sure, HIV treatment with three drugs is more expensive than one or two for PrEP, but it strikes me that the double benefit (i.e., to the individual and the uninfected partner) easily justifies the incremental cost.

If the final results of 052 are as impressive as the glimpse we’ve received thus far, one could see oral PrEP becoming a strategy limited to high-risk individuals who do not have steady partners (e.g., MSM similar to those in iPrEx, or certain individual from hyperendemic areas).

Which means that the best way to prevent HIV with meds is usually to treat those who have it — and only rarely to treat those who don’t.

8 Responses to “More Favorable Results on PrEP, But …”

  1. Louiselle LeBlanc says:

    Thank you Dr Sax for this important message. I have recently returned from 2 years of HIV clinical services implementation/capacity building as well as policies advisory in 2 African countries. I am still dumbfounded that we haven’t yet succeeded in achieving national guideline and policies changes for treating serodiscordant couples, not even for HIV-positive men when their HIV-negative female partner was pregnant or breastfeeding (which I regularly saw in my practice)! So I agree with you 100% that we need to start treating all HIV-infected individuals before treating HIV-negative people.
    Also of concern to me is talking about giving TDF to uninfected individuals when the majority of Africans are still taking thymidine analogues! National guidelines are only now starting to change to TDF as first choice drug (keeping AZT as equivalent as they are not sure they will be able to maintain the supply of TDF). With no means to detect early failure, patients often remain on a failing thymidine/NNRTI regimen for years (never had genotypes so could only guess the number of TAMs) – and with TDF/3TC/lopinavir-ritonavir as the only available remaining drugs, how sustainable can we be?
    So for resource-limited settings: #1- treat all positive individuals (prioritizing serodiscordant couples if money is an issue); #2- ensure TDF is recommended as the preferred first-line drug (and is available for health-care providers); and then, if there are still drugs left – treat the high-risk HIV-negative.

  2. Paul Sax says:

    Louiselle, what a great comment! I couldn’t agree more, thank you for raising these additional drug-related resource issues.


  3. Robert Reinhard says:

    Dear Dr. Sax
    I think your opinion is a little too black and white when using all options available to us have finally reached a point where treatment and prevention are not at odds but work together.
    : 1) in the Partners study, the results were obtained from couples in which the HIV positive partner was at a stage of infection where ART was not yet recommended under guidelines but they were given ART if it became necessary and some did, 2) the conclusion of the Partners study is not to place all negative individuals in all serodiscordant couples on ART but that local situatins will evaluate, after more demonstration research, whether PrEP can be part of a mix of options that the couple itself may decide works best or better for them, and 3) using results from TDF2, we can appreciate that many individuals are not in “exclusive” couples and that individuals can benefit from protection when they have sex outside of their relationships. The results of these studies are powerful. The fact that the levels of protection were observed early enough to halt the trial shows that as part of a mix of efforts- including implementation of the o52 results, circumcision, standard behavioralprevnetion, and other means, local efforts have multiple ways to use what’s at hand

  4. Paul Sax says:

    Robert, fair points all — best to use all strategies available to us for prevention. But I’d hate to see someone not able to access ART due to its diversion for PrEP, this does not seem logical to me.


  5. Terry Hall says:

    Hi Dr Sax, i went back to read the study design to see the role of condoms. Since the pts were given condoms and counselling, i am unsure how much taking the meds made the + partner feel they didn’t have to use condoms, or if not using condoms is the regular practice. Is not using condoms a surrogate for the likely adherence of the + partner?
    i also agree with Louiselle for a framework to forge policy, but as always individuals will make their own decisions.

  6. Dr Sax, your points are well made, as are those of your correspondents. However, I wonder if any provision will be made for non-sexual HIV transmission?

    Here in Tanzania, everyone with HIV or with HIV positive partners is assumed to be infected through or at risk of sexually transmitted HIV. Yet non-sexual transmission is also a considerable risk.

    Nigeria recently revealed that most transfused blood comes from paid donors, contrary to the national guidelines. Similar claims have been made about transfused blood in Tanzania and other African countries.

    Will non-sexual transmission become buried under the euphoria that comes with the availability of yet more drugs?

    If money and resources are scarce, vastly multiplying the amount of drugs prescribed in high prevalence countries will not be the most cost effective strategy. And it may fail to prevent a substantial proportion of transmission.

  7. verkuyl says:

    Problem is of course all those people who are HIV + and are not tested so they can’t be given ARV treatment to reduce infectivity or don’t want to take the drugs. Next step ARV in drinking water or perhaps better in beer?

  8. Eduardo Pozzobon says:

    Compare PrEp with condom use and you will see that condom use is: 1. Less expensive; 2. Devoided of collateral effects; 3. More efficacious than PrEP, if you adhere to it (as PrEP). So, why to use this strategy? I think drugs should be reserved for infected people or for post exposure prophylaxis. All these studies proof that it works, but it’s unrealistic to use this strategy in developing countries.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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