Celum, C.Wald, A.Lingappa, J.R.Magaret, A.S.Wang, R.S.Mugo, N.Mujugira, A.Baeten, J.M.Mullins, J.I.Hughes, J.P.Bukusi, E.A.Cohen, C.R.Katabira, E.Ronald, A.Kiarie, J.Farquhar, C.Stewart, G.J.Makhema, JosephEssex, MyronWere, E.Fife, K.H.de Bruyn, G.Gray, G.E.McIntyre, J.A.Manongi, R.Kapiga, S.Coetzee, D.Allen, S.Inambao, M.Kayitenkore, K.Karita, E.Kanweka, W.Delany, S.Rees, H.Vwalika, B.Stevens, W.Campbell, M.S.Thomas, K.K.Coombs, R.W.Morrow, R.Whittington, W.L.H.McElrath, M.J.Barnes, L.Ridzon, R.Corey, L.2016-04-212010Celum, C., A. Wald, J.R. Lingappa, A.S. Magaret, R.S. Wang, N. Mugo, A. Mujugira, et al. 2010. “Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2.” N Engl J Med 362 (5) (February 4): 427–439. doi:10.1056/nejmoa0904849.0028-4793http://nrs.harvard.edu/urn-3:HUL.InstRepos:26718771BACKGROUND: 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, > or = 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 log(10) 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 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2.en-USJournal Article2016-04-2110.1056/NEJMoa0904849