Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)-Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2-Coinfected Individuals

J Infect Dis. 2016 May 15;213(10):1573-8. doi: 10.1093/infdis/jiv765. Epub 2015 Dec 23.


Background: Immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2).

Methods: We evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated.

Results: GUD incidence increased from 15.0 episodes per 100 person-years before ART to 26.9 episodes per 100 person-years in the first full quarter after ART initiation (IRR, 1.83;P= .03), and the incidence of HSV-2-associated GUD increased from 8.1 to 19.0 episodes per 100 person-years (IRR, 2.20;P= .02). Subsequently, the incidence of GUD was similar to that before ART, although the numbers were small. Persons receiving suppressive acyclovir had fewer GUD episodes, but the IRR after beginning ART was similar in the acyclovir and placebo groups.

Conclusions: Initiation of ART in HIV/HSV-2-coinfected persons is associated with a transient increase in GUD and HSV-2 GUD. Acyclovir reduces the incidence of GUD but does not prevent an increase in GUD incidence during the first quarter following initiation of ART.

Keywords: acyclovir; antiretroviral therapy; herpes simplex virus; human immunodeficiency virus.

Publication types

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

MeSH terms

  • Acyclovir / adverse effects
  • Acyclovir / therapeutic use
  • Adult
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Coinfection
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • Herpes Genitalis / complications
  • Herpes Genitalis / drug therapy*
  • Herpes Genitalis / epidemiology
  • Herpesvirus 2, Human / isolation & purification*
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / drug therapy
  • Immune Reconstitution Inflammatory Syndrome / epidemiology*
  • Incidence
  • Male
  • Middle Aged
  • Ulcer / complications
  • Ulcer / drug therapy
  • Ulcer / epidemiology*


  • Acyclovir