Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in Botswana

作者：Thigpen, Michael C.^*; Kebaabetswe, Poloko M.; Paxton, Lynn A.; Smith, Dawn K.; Rose, Charles E.; Segolodi, Tebogo M.; Henderson, Faith L.; Pathak, Sonal R.; Soud, Fatma A.; Chillag, Kata L.; Mutanhaurwa, Rodreck; Chirwa, Lovemore Ian; Kasonde, Michael; Abebe, Daniel; Buliva, Evans; Gvetadze, Roman J.; Johnson, Sandra; Sukalac, Thom; Thomas, Vasavi T.; Hart, Clyde; Johnson, Jeffrey A.; Malotte, C. Kevin; Hendrix, Craig W.; Brooks, John T.

来源：New England Journal of Medicine, 2012, 367(5): 423-434.

DOI：10.1056/NEJMoa1110711

• TENOFOVIR DISOPROXIL FUMARATE
• PREVENTION
• EMTRICITABINE
• INFECTION
• TRIALS

Background @@@ Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. @@@ Methods @@@ We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. @@@ Results @@@ A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P = 0.008), and dizziness (15.1% vs. 11.0%, P = 0.03) than the placebo group, but the rates of serious adverse events were similar (P = 0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P = 0.03). @@@ Conclusions @@@ Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.)

• 出版日期2012-8-2