|Preexposure Prophylaxis with Oral Tenofovir or Tenofovir/Emtricitabine|
|HIV Meds Quarterly Research Brief|
|Susa Coffey, MD, HIV InSite Medical Editor|
Preexposure prophylaxis (PrEP) using oral tenofovir/emtricitabine was demonstrated last year, in the iPrEx study, to significantly reduce the risk of HIV infection in HIV-seronegative men who have sex with men (MSM). At the recent 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention, results from 2 large randomized, double-blind studies show that oral PrEP also is effective in preventing infection in heterosexual women and men.
The Partners PrEP study, conducted in Kenya and Uganda, enrolled nearly 5,000 serodiscordant heterosexual couples in which the HIV-infected partner was not eligible for ART. The seronegative partner was randomized to 1 of 3 study arms: tenofovir, tenofovir/emtricitabine, or placebo, to be taken once daily. With up to 36 months of follow-up, significantly fewer HIV infections were found in each of the 2 active ARV arms than in the placebo arm. Efficacy of tenofovir and of tenofovir/emtricitabine were 62% and 73%, respectively, with no statistical difference between the ARV arms, or between women and men.(1)
The TDF2 Study randomized 1,200 HIV-uninfected heterosexual women and men in Botswana to daily oral tenofovir/emtricitabine or to placebo. In this study, the protective efficacy of tenofovir/emtricitabine was 63% (p = .013), and although low numbers of seroconversions precluded definitive analyses by sex, PrEP appeared to be effective in both women and men.(2)
In general, PrEP was well tolerated. Adverse effects included mild nausea in the initial weeks of PrEP but no significant renal or other toxicity. Partners PrEP reported no difference in pregnancy rates in the study arms. Overall, study participants appeared to decrease their HIV risk behaviors over time.
Researchers from the iPrEx study also presented an update on their data at the conference. Particularly notable findings included additional evidence that PrEP efficacy is strongly related to adherence, and that PrEP did not appear to be effective in the subgroup of transgender women who have sex with men.(3)
| Clinical bottom line|
Partners PrEP and TDF2, as with the previously reported iPrEx study of oral tenofovir/emtricitabine in MSM and the Caprisa 004 study of tenofovir gel in heterosexual women, confirm that ARV-based preexposure prophylaxis can significantly lower the risk of sexual acquisition of HIV (though efficacy has not been demonstrated in transgender women and further study is needed). Importantly, Partners PrEP and TDF2 demonstrate that oral PrEP was effective in both women and men, in contrast to the FEM-PrEP study of high-risk, HIV-uninfected women, which was halted earlier this year because of lack of efficacy.
It should be noted that, in each of these studies, ARV PrEP was given in conjunction with comprehensive packages of risk-reduction interventions, including adherence support, risk-reduction counseling, condom provision, and HIV testing, and that these likely are important components in preventing HIV infection. Strategies for "real life" use of PrEP have yet to be explored.
There is no information at present on efficacy of oral PrEP in several important risk populations, such as injection drug users, and very limited information in some others (eg, transgender women). There also is no information on topical PrEP in MSM or transgender women. Further studies are under way. Although the role that PrEP will play in prevention strategies in the United States is not yet clear, it is likely to be a useful tool for appropriate individuals, and, importantly, one that will be in the control of the at-risk HIV-uninfected individual. The CDC is developing guidance on use of PrEP in the United States.
Note that the HPTN 052 study, also presented at the conference and recently published, demonstrated that ARV therapy, given to the HIV-infected partner in a serodiscordant relationship, reduced HIV transmission to the uninfected partner by 96%.(4)
1. Baeten J. Antiretroviral pre-exposure prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP study. In: Program and abstracts of the 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome. Abstract MOAX0106.
2. Thigpen MC, Kebaabetswe PM, Smith DK, et al; TDF2 Study Group. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study. In: Program and abstracts of the 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome. Abstract WELBC01.
3. Grant R, McMahan V, Liu A, et al; iPrEx Study Team. Completed observation of the randomized placebo-controlled phase of iPrEx: daily oral FTC/TDF pre-exposure HIV prophylaxis among men and trans women who have sex with men. In: Program and abstracts of the 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome. Abstract WELBC04.
4. Cohen MS, Chen YQ, McCauley M, et al; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505.