Effect of HSV-2 serostatus on acquisition of HIV by young men: results of a longitudinal study in Orange Farm, South Africa

J Infect Dis. 2009 Apr 1;199(7):958-64. doi: 10.1086/597208.


Background: The objectives of this study were to assess the impact among young men of herpes simplex virus type 2 (HSV-2) status on the acquisition of human immunodeficiency virus (HIV) and on the protective effect of male circumcision against HIV acquisition.

Methods: We used data collected during a male circumcision trial conducted in Orange Farm, South Africa. We estimated adjusted incidence rate ratios (IRRs) for HIV acquisition, using survival analysis and background characteristics, HSV-2 status, male circumcision status, and sexual behavior as covariates.

Results: Compared with subjects who remained HSV-2 negative throughout the study, subjects who were HSV-2 positive at enrollment had an adjusted IRR of 3.3 (95% confidence interval [CI], 1.5-7.4; P=.004), and those who became HSV-2 positive during follow-up had an adjusted IRR of 7.0 (95% CI, 3.9-12.4; P<.001). The population fraction of incident HIV infection attributable to HSV-2 was 27.8% (95% CI, 17.7%-37.2%). Intention-to-treat analysis of the protective effect of male circumcision on HIV acquisition was the same among men with and men without HSV-2 (0.38 vs. 0.37; P=.93).

Conclusions: This study shows that HSV-2 has a substantial impact on HIV acquisition among young South African men. It suggests that HSV-2 infection enhances HIV acquisition and is responsible for approximately 25% of incident cases of HIV infection. However, the protective effect of male circumcision against HIV acquisition appears independent of HSV-2 serostatus.

Trial registration: ClinicalTrials.gov identifier: NCT00122525.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood*
  • Circumcision, Male
  • HIV Infections / epidemiology
  • HIV Infections / etiology*
  • HIV Infections / prevention & control
  • HIV-1
  • Herpes Genitalis / complications*
  • Herpes Genitalis / epidemiology
  • Herpes Genitalis / immunology
  • Herpesvirus 2, Human / immunology*
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Risk Factors
  • South Africa / epidemiology
  • Young Adult


  • Antibodies, Viral

Associated data

  • ClinicalTrials.gov/NCT00122525