Introduction Antiretroviral pre-exposure prophylaxis (PrEP) reduces the incidence of acquisition of human immunodeficiency virus type 1 (HIV-1) in men who have sex with men and is a promising approach for preventing HIV-1 in heterosexual populations. Methods We conducted a randomized, three-arm trial of oral antiretroviral PrEP among heterosexual couples from Kenya and Uganda in which one member was HIV-1 seronegative and the other HIV-1 seropositive. Seronegative partners were randomly assigned to once-daily tenofovir (TDF), combination emtricitabine/tenofovir (FTC/TDF), or matching placebo and followed monthly for up to 36 months. At enrollment, HIV-1 seropositive partners were not eligible for antiretroviral therapy under national guidelines. All couples received standard HIV-1 treatment and prevention services, including individual and couples risk-reduction counseling and condoms. Results 4758 couples were enrolled; for 62%, the HIV-1 seronegative partner was male. For HIV-1 seropositive participants, the median CD4 count was 495 cells/μL (interquartile range 375–662). Of 82 post-randomization HIV-1 infections, 17 were among those assigned TDF (incidence 0.65 per 100 person-years), 13 among those assigned FTC/TDF (incidence 0.50 per 100 person-years), and 52 among those assigned placebo (incidence 1.99 per 100 person-years), indicating a 67% relative reduction in HIV-1 incidence for TDF (95% CI 44 to 81, p<0.001) and 75% for FTC/TDF (95% CI 55 to 87, p<0.001). HIV-1 protective effects of FTC/TDF and TDF were not significantly different (p=0.23), and both study medications significantly reduced HIV-1 incidence in both men and women. The rate of serious medical events was similar across the study arms. Conclusions Oral TDF and FTC/TDF provided substantial protection against HIV-1 acquisition in heterosexual men and women, with comparable efficacy of TDF and FTC/TDF. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number NCT00557245)

BACKGROUND Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, ≥250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P = 0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log10 copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2–positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log10 copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Summary Background Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. Methods We followed 3790 heterosexual HIV-1 serodiscordant couples from seven African countries participating in two longitudinal HIV-1 incidence studies. Among hormonal contraceptive users (including injectable and oral contraceptive users) and nonusers, we compared rates of HIV-1 acquisition in women and HIV-1 transmission from women to men. Findings Among 1314 couples in which the HIV-1 seronegative partner was female, HIV-1 acquisition rates were 6.61 and 3.78 per 100 person-years among hormonal contraceptive users and nonusers (adjusted hazard ratio [AHR]=1.98, 95% confidence interval [CI] 1.06–3.68, p=0.03). Among 2476 couples in which the HIV-1 seronegative partner was male, HIV-1 transmission rates from women to men were 2.61 and 1.51 per 100 person-years in those whose partners currently used versus did not use hormonal contraception (AHR=1.97, 95% CI 1.12–3.45, p=0.02). In subgroup analysis, injectable contraceptive users had increased risk for acquiring and transmitting HIV-1 to their partner and HIV-1 seropositive women using injectable contraception had higher genital HIV-1 RNA concentrations, suggesting a mechanism for increased transmission risk. Oral contraceptives were used too infrequently to draw definitive conclusions about HIV-1 risk. Interpretation Women should be counseled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, particularly injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or lower-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. Funding National Institutes of Health (R03 HD068143, R01 AI083034, P30 AI027757, and T32 AI007140) and the Bill and Melinda Gates Foundation (26469 and 41185).

We evaluated performance, accuracy, and acceptability parameters of unsupervised oral fluid (OF) HIV self-testing (HIVST) in a general population in western Kenya. In a prospective validation design, we enrolled 240 adults to perform rapid OF HIVST and compared results to staff administered OF and rapid fingerstick tests. All reactive, discrepant, and a proportion of negative results were confirmed with lab ELISA. Twenty participants were video-recorded conducting self-testing. All participants completed a staff administered survey before and after HIVST to assess attitudes towards OF HIVST acceptability. HIV prevalence was 14.6 %. Thirty-six of the 239 HIVSTs were invalid (15.1 %; 95 % CI 11.1–20.1 %), with males twice as likely to have invalid results as females. HIVST sensitivity was 89.7 % (95 % CI 73–98 %) and specificity was 98 % (95 % CI 89–99 %). Although sensitivity was somewhat lower than expected, there is clear interest in, and high acceptability (94 %) of OF HIV self-testing.