Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2


Celum, C; Wald, A; Lingappa, JR; Magaret, AS; Wang, RS; Mugo, N; Mujugira, A; Baeten, JM; Mullins, JI; Hughes, JP; Bukusi, EA; Cohen, CR; Katabira, E; Ronald, A; Kiarie, J; Farquhar, C; Stewart, GJ; Makhema, J; Essex, M; Were, E; Fife, KH; de Bruyn, G; Gray, GE; McIntyre, JA; 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, MS; Thomas, KK; Coombs, RW; Morrow, R; Whittington, WLH; McElrath, MJ; Barnes, L; Ridzon, R; Corey, L; Partners in Prevention HSV/, HIVTransmissionStudyTeam; (2010) Acyclovir and Transmission of HIV-1 from Persons Infected with HIV-1 and HSV-2. The New England journal of medicine, 362 (5). pp. 427-439. ISSN 0028-4793 DOI: https://doi.org/10.1056/NEJMoa0904849

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Abstract

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 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 log10 copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2.

Item Type: Article
Keywords: herpes-simplex-virus, human-immunodeficiency-virus, placebo-controlled, trial, discordant couples, clinical-trials, double-blind, type-1, women, suppression, plasma, AIDS-Related Opportunistic Infections, drug therapy, Acyclovir, adverse effects, therapeutic use, Adolescent, Adult, Antiviral Agents, adverse effects, therapeutic use, CD4 Lymphocyte Count, Female, Follow-Up Studies, HIV Infections, complications, transmission, HIV-1, genetics, isolation & purification, Herpes Genitalis, complications, drug therapy, Herpesvirus 2, Human, Humans, Intention to Treat Analysis, Kaplan-Meiers Estimate, Male, Patient Compliance, Pregnancy, RNA, Viral, blood, Unsafe Sex, statistics & numerical data, Young Adult
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 20089951
Web of Science ID: 274193300008
URI: http://researchonline.lshtm.ac.uk/id/eprint/4079

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