title: Effect of herpes simplex suppression on incidence of HIV among women in Tanzania.
abstract: BACKGROUND
  Infection with herpes simplex virus type 2 (HSV-2) is associated with an increased risk of acquiring infection with the human immunodeficiency virus (HIV). This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition.
  
  
  METHODS
  Female workers at recreational facilities in northwestern Tanzania who were 16 to 35 years of age were interviewed and underwent serologic testing for HIV and HSV-2. We enrolled female workers who were HIV-seronegative and HSV-2-seropositive in a randomized, double-blind, placebo-controlled trial of suppressive treatment with acyclovir (400 mg twice daily). Participants attended mobile clinics every 3 months for a follow-up period of 12 to 30 months, depending on enrollment date. The primary outcome was the incidence of infection with HIV. We used a modified intention-to-treat analysis; data for participants who became pregnant were censored. Adherence to treatment was estimated by a tablet count at each visit.
  
  
  RESULTS
  A total of 821 participants were randomly assigned to receive acyclovir (400 participants) or placebo (421 participants); 679 (83%) completed follow-up. Mean follow-up for the acyclovir and placebo groups was 1.52 and 1.62 years, respectively. The incidence of HIV infection was 4.27 per 100 person-years (27 participants in the acyclovir group and 28 in the placebo group), and there was no overall effect of acyclovir on the incidence of HIV (rate ratio for the acyclovir group, 1.08; 95% confidence interval, 0.64 to 1.83). The estimated median adherence was 90%. Genital HSV was detected in a similar proportion of participants in the two study groups at 6, 12, and 24 months. No serious adverse events were attributable to treatment with acyclovir.
  
  
  CONCLUSIONS
  These data show no evidence that acyclovir (400 mg twice daily) as HSV suppressive therapy decreases the incidence of infection with HIV. (Current Controlled Trials number, ISRCTN35385041 [controlled-trials.com].).
authors.affiliation: London School of Hygiene and Tropical Medicine, London. deborah.watson-jones@lshtm.ac.uk
authors.forename: Deborah
authors.initials: D
authors.lastname: Watson-Jones
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.forename: Mary
authors.initials: M
authors.lastname: Rusizoka
authors.forename: John
authors.initials: J
authors.lastname: Changalucha
authors.forename: Kathy
authors.initials: K
authors.lastname: Baisley
authors.forename: Kokugonza
authors.initials: K
authors.lastname: Mugeye
authors.forename: Clare
authors.initials: C
authors.lastname: Tanton
authors.forename: David
authors.initials: D
authors.lastname: Ross
authors.forename: Dean
authors.initials: D
authors.lastname: Everett
authors.forename: Tim
authors.initials: T
authors.lastname: Clayton
authors.forename: Rebecca
authors.initials: R
authors.lastname: Balira
authors.forename: Louise
authors.initials: L
authors.lastname: Knight
authors.forename: Ian
authors.initials: I
authors.lastname: Hambleton
authors.forename: Jerome
authors.initials: J
authors.lastname: Le Goff
authors.forename: Laurent
authors.initials: L
authors.lastname: Belec
authors.forename: Richard
authors.initials: R
authors.lastname: Hayes
mesh_terms: D000212:Acyclovir / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005836:Genitalia, Female / Q000821:virology; D006678:HIV; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control*; D006558:Herpes Genitalis / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D010349:Patient Compliance; D012725:Sexual Behavior; D013636:Tanzania / Q000453:epidemiology
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D015483:HIV Antibodies; D000212:Acyclovir