The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics

J Acquir Immune Defic Syndr. 2004 Apr 15;35(5):435-45. doi: 10.1097/00126334-200404150-00001.


Increasing evidence demonstrates a substantial link between the epidemics of sexually transmitted HIV-1 and herpes simplex virus (HSV)-2 infection. More than 30 epidemiologic studies have demonstrated that prevalent HSV-2 is associated with a 2- to 4-fold increased risk of HIV-1 acquisition. Per-sexual contact transmission rates among couples from Rakai, Uganda indicate that at all levels of plasma HIV-1 RNA in the source partner, HSV-2-seropositive HIV-1-susceptible persons have a 5-fold greater risk of acquiring HIV-1 compared with HSV-2-negative persons. In vitro and in vivo studies suggest that mucosal HIV-1 shedding is more frequent and in greater amounts during mucocutaneous HSV-2 replication, including subclinical mucosal reactivations. Most HIV-1-infected persons are coinfected with HSV-2, and most experience frequent subclinical and clinical reactivations of HSV-2. Subclinical HSV reactivation elevates serum HIV-1 RNA levels, and daily therapy with acyclovir appears to reduce plasma HIV-1 RNA. These data show that greater attention to the diagnosis and treatment of HSV-2 among HIV-1-infected persons is warranted, especially those who continue to be sexually active, those not on antiretroviral therapy, or those whose disease is not well suppressed by antiretrovirals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acyclovir / therapeutic use
  • Antibodies, Viral / blood
  • Clinical Trials as Topic
  • Comorbidity
  • Disease Transmission, Infectious
  • Female
  • Global Health*
  • HIV Infections* / epidemiology
  • HIV Infections* / transmission
  • HIV-1* / pathogenicity
  • HIV-1* / physiology
  • Herpes Simplex* / diagnosis
  • Herpes Simplex* / drug therapy
  • Herpes Simplex* / epidemiology
  • Herpes Simplex* / transmission
  • Herpesvirus 2, Human* / immunology
  • Herpesvirus 2, Human* / physiology
  • Humans
  • Male
  • Prevalence
  • Risk Factors
  • Viral Load
  • Virulence
  • Virus Replication


  • Antibodies, Viral
  • Acyclovir