Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.

BACKGROUND: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. METHODS: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. RESULTS: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). CONCLUSIONS: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.).

The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in Individuals With Active Hepatitis B.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were evaluated. METHODS: The Iniciativa Profilaxis Pre-Exposición study randomized 2499 HIV-negative men and transgender women who have sex with men to once-daily oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained at screening and at the time PrEP was discontinued. HBV DNA was assessed by polymerase chain reaction, and drug resistance was assessed by population sequencing. Vaccination was offered to individuals susceptible to HBV infection. RESULTS: Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF) had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the active arm had liver function tests performed at follow-up. Liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain reaction of stored samples showed that 2 participants in the active arm had evidence of acute HBV infection at enrollment. Both had evidence of grade 4 transaminase elevations with subsequent resolution. Overall, there was no evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the series. CONCLUSIONS: PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. HBV vaccination rates at screening were low globally, despite recommendations for its use, yet uptake and efficacy were high when offered.