Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana
Thigpen, M.C.; Kebaabetswe, P.M.; Paxton, L.A.; Smith, D.K.; Rose, C.E.; Segolodi, T.M.; Henderson, F.L.; Pathak, S.R.; Soud, F.A.; Chillag, K.L.; Mutanhaurwa, R.; Chirwa, L.Ian.; Kasonde, M.; Abebe, D.; Buliva, E.; Gvetadze, R.J.; Johnson, S.; Sukalac, T.; Thomas, V.T.; Hart, C.; Johnson, J.A.; Malotte, C.Kevin.; Hendrix, C.W.; Brooks, J.T.; Toomey, K.; Davis, M.; Shepherd, J.; Sukalac, T.; Abebe, D.; Baakile, K.; Balopi, W.; Bolobilwe, O.; Buliva, E.; Byrd, D.; Casillas, P.; Chanda, J.; Chilum
New England Journal of Medicine 367(5): 423-434
2012
ISSN/ISBN: 0028-4793 PMID: 22784038 DOI: 10.1056/nejmoa1110711Document Number: 553039
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. 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. 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). 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.).