title: Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the Step study).
abstract: BACKGROUND
  Extensive observational data suggest that herpes simplex virus type 2 (HSV-2) infection may facilitate HIV acquisition, increase HIV viral load, and accelerate HIV progression and onward transmission. To explore these relationships, we examined the impact of preexisting HSV-2 infection in an international HIV vaccine trial.
  
  
  METHODS
  We analyzed the associations between prevalent HSV-2 infection and HIV-1 acquisition and progression among 1836 men who have sex with men. We used Cox proportional hazards regression models to estimate the association between HSV-2 infection and both HIV acquisition and antiretroviral therapy (ART) initiation, and linear regression to explore the effect of HSV-2 on pre-ART viral load.
  
  
  RESULTS
  HSV-2 infection increased risk of HIV-1 acquisition among all volunteers [adjusted hazard ratio 2.2; 95% confidence interval (CI): 1.4 to 3.5]. Adjusting for demographic variables, circumcision, Ad5 titer, and significant risk behaviors, the risk of HIV acquisition among HSV-2-infected placebo recipients was 3-fold higher than HSV-2 seronegatives (adjusted hazard ratio 3.3; 95% CI: 1.6 to 6.9). Past HSV-2 infection was associated with a 0.2 log10 copies per milliliter higher adjusted mean set point viral load (95% CI: 0.3 lower to 0.6 higher). HSV-2 infection was not associated with time to ART initiation.
  
  
  CONCLUSIONS
  Among men who have sex with men in an HIV-1 vaccine trial, preexisting HSV-2 infection was a major risk factor for HIV acquisition. Past HSV-2 did not significantly increase HIV viral load or early disease progression. HSV-2-seropositive persons will likely prove more difficult than HSV-2-seronegative persons to protect against HIV infection using vaccines or other prevention strategies.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA. rbarnaba@uw.edu
authors.forename: Ruanne V
authors.initials: RV
authors.lastname: Barnabas
authors.forename: Judith N
authors.initials: JN
authors.lastname: Wasserheit
authors.forename: Yunda
authors.initials: Y
authors.lastname: Huang
authors.forename: Holly
authors.initials: H
authors.lastname: Janes
authors.forename: Rhoda
authors.initials: R
authors.lastname: Morrow
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fuchs
authors.forename: Karen E
authors.initials: KE
authors.lastname: Mark
authors.forename: Martin
authors.initials: M
authors.lastname: Casapia
authors.forename: Devan V
authors.initials: DV
authors.lastname: Mehrotra
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control* / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology*; D006561:Herpes Simplex / Q000150:complications* / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019562:Viral Load; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents