Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: A randomized controlled trial

Andrew Mujugira, Amalia S. Magaret, Connie Celum, Jared M. Baeten, Jairam R. Lingappa, Rhoda Ashley Morrow, Kenneth H. Fife, Sinead Delany-Moretlwe, Guy De Bruyn, Elizabeth A. Bukusi, Etienne Karita, Saidi Kapiga, Lawrence Corey, Anna Wald, Mary Campbell, Robert W. Coombs, James P. Hughes, M. Juliana Mcelrath, James I. Mullins, David CoetzeeEdwin Were, Max Essex, Joseph Makhema, Elly Katabira, Allan Ronald, Susan Allen, Kayitesi Kayitenkore, Craig Cohen, William Kanweka, Bellington Vwalika, Rachel Manongi, Carey Farquhar, Grace John-Stewart, James Kiarie, Mubiana Inambao, Helen Rees, Glenda Gray, James Mcintyre, Nelly Rwamba Mugo

Research output: Contribution to journalArticle

21 Scopus citations


Background. Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2-serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown.Methods. Within a randomized trial of daily acyclovir 400 mg twice daily in African HIV-1 serodiscordant couples, in which the HIV-1-infected partner was HSV-2 seropositive, we identified partnerships in which HIV-1-susceptible partners were HSV-2 seronegative to estimate the effect of acyclovir on risk of HSV-2 transmission.Results. We randomly assigned 911 HSV-2/HIV-1-serodiscordant couples to daily receipt of acyclovir or placebo. We observed 68 HSV-2 seroconversions, 40 and 28 in acyclovir and placebo groups, respectively (HSV-2 incidence, 5.1 cases per 100 person-years; hazard ratio [HR], 1.35 [95% confidence interval,. 83-2.20]; P =. 22). Among HSV-2-susceptible women, vaginal drying practices (adjusted HR, 44.35; P =. 004) and unprotected sex (adjusted HR, 9.91; P =. 002) were significant risk factors for HSV-2 acquisition; having more children was protective (adjusted HR, 0.47 per additional child; P =. 012). Among HSV-2-susceptible men, only age ≤30 years was associated with increased risk of HSV-2 acquisition (P =. 016).Conclusions. Treatment of African HSV-2/HIV-1-infected persons with daily suppressive acyclovir did not decrease risk of HSV-2 transmission to susceptible partners. More-effective prevention strategies to reduce HSV-2 transmission from HIV-1-infected persons are needed.

Original languageEnglish (US)
Pages (from-to)1366-1374
Number of pages9
JournalJournal of Infectious Diseases
Issue number9
StatePublished - Nov 1 2013



  • acyclovir
  • Africa
  • HIV-1
  • HSV-2
  • serodiscordant couples
  • transmission

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Mujugira, A., Magaret, A. S., Celum, C., Baeten, J. M., Lingappa, J. R., Morrow, R. A., Fife, K. H., Delany-Moretlwe, S., De Bruyn, G., Bukusi, E. A., Karita, E., Kapiga, S., Corey, L., Wald, A., Campbell, M., Coombs, R. W., Hughes, J. P., Mcelrath, M. J., Mullins, J. I., ... Rwamba Mugo, N. (2013). Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: A randomized controlled trial. Journal of Infectious Diseases, 208(9), 1366-1374. https://doi.org/10.1093/infdis/jit333