Tenofovir Helps Prevent Herpes Simplex Virus Type 2 Infection
Originally published in the New England Journey of Medecine
Salim S. Abdool Karim, M.B., Ch.B., Ph.D., Quarraisha Abdool Karim, Ph.D., Ayesha B.M. Kharsany, Ph.D., Cheryl Baxter, Ph.D., Anneke C. Grobler, Ph.D., Lise Werner, M.Sc., Angela Kashuba, Pharm.D., Leila E. Mansoor, Ph.D., Natasha Samsunder, B.Tech., Adrian Mindel, M.D., and Tanuja N. Gengiah, Ph.D. for the CAPRISA 004 Trial Group
N Engl J Med 2015; 373:530-539August 6, 2015DOI: 10.1056/NEJMoa1410649
Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections.
We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2–negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing.
The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P=0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P=0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P=0.005).
In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number,NCT00441298.)
Presented in part at the XVIII International AIDS Conference, Vienna, July 18–23, 2010.
The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial and the herpes simplex virus type 2 (HSV-2) substudy were supported by the U.S. Agency for International Development, FHI 360 (cooperative agreement GPO-A-00-05-00022-00, contract 132119), and the Technology Innovation Agency, the biotechnology organization of the Department of Science and Technology of the South African government. The CAPRISA 004 trial and the HSV-2 substudy were also supported by CONRAD for product manufacturing and packaging and by grants from the U.S. National Institutes of Health Comprehensive International Program of Research on AIDS (AI51794) and the Columbia University–Southern African Fogarty AIDS International Training and Research Programme (D43TW00231) for research infrastructure and training.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Drs. Salim S. Abdool Karim and Quarraisha Abdool Karim contributed equally to this article.
We thank Drs. James Rooney and Tomas Cihlar for their assistance with information and data on tenofovir for the HSV-2 prevention hypothesis and Professor Rhoda Morrow for conducting the Western blot testing.
From the Centre for the AIDS Programme of Research in South Africa (CAPRISA) (S.S.A.K., Q.A.K., A.B.M.K., C.B., A.C.G., L.W., L.E.M., N.S., A.M., T.N.G.) and the University of KwaZulu-Natal (S.S.A.K.) — both in Durban, South Africa; the Department of Epidemiology, Mailman School of Public Health, Columbia University, New York (S.S.A.K., Q.A.K.); and the Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill (A.K.).
Address reprint requests to Dr. Salim Abdool Karim at CAPRISA, 2nd Fl., Doris Duke Medical Research Institute, Private Bag X7, Congella, 4013, South Africa, or at email@example.com.
A complete list of investigators in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 Trial is provided in the Supplementary Appendix, available at NEJM.org.