title: Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)-Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2-Coinfected Individuals.
abstract: 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.
authors.affiliation: Department of Medicine Deparment of Microbiology and Immunology Department of Pathology, Indiana University, Indianapolis.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Fife
authors.affiliation: Department of Epidemiology.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mugwanya
authors.affiliation: Department of Global Health.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Thomas
authors.affiliation: Department of Epidemiology Department of Global Health Department of Medicine.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.affiliation: Department of Epidemiology Department of Global Health Department of Medicine.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.affiliation: Center for Microbiology Research, Kenya Medical Research Institute, Nairobi.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bukusi
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania.
authors.forename: Guy
authors.initials: G
authors.lastname: de Bruyn
authors.affiliation: Department of Epidemiology Department of Global Health.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mujugira
authors.affiliation: Department of Obstetrics and Gynaecology, University of Zambia, and Zambia-Emory HIV Research Project, Lusaka.
authors.forename: Bellington
authors.initials: B
authors.lastname: Vwalika
authors.affiliation: Department of Epidemiology Department of Medicine Department of Laboratory Medicine, University of Washington, and Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.affiliation: Department of Global Health Department of Medicine Department of Pediatrics.
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
mesh_terms: D000212:Acyclovir / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000188:drug therapy / Q000453:epidemiology*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D014456:Ulcer / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*
chemical_list: D000212:Acyclovir
keywords: acyclovir; antiretroviral therapy; herpes simplex virus; human immunodeficiency virus