title: Herpes simplex virus type 2 coinfection does not accelerate CD4 count decline in untreated HIV infection.
abstract: BACKGROUND
  Herpes simplex virus type 2 (HSV-2) reactivations are associated with increased HIV load, but whether HSV-2 coinfection accelerates HIV disease is unclear. We compared rates of CD4 count decline according to HSV-2 status in untreated HIV-infected adults.
  
  
  METHODS
  HIV-infected patients with a past period of antiretroviral therapy (ART)-untreated follow-up with initial CD4 count of 400-900 cells/mm(3) and no chronic anti-HSV therapy were included. HSV-2 status was determined by HerpeSelect enzyme-linked immunosorbent assay. Rates of CD4 count change were compared by HSV-2 status using mixed linear regression models, and time to the first of ART initiation or CD4 <350 cells/mm(3) using proportional hazards models.
  
  
  RESULTS
  Of 218 patients included, 123 (56.4%) were seropositive for HSV-2 and 161 (73.8%) for HSV-1. In univariate analysis, the difference in the rate of CD4 count change associated with HSV-2 was not statistically significant at +13.6 cells/mm(3)/year (P = .12). Results were similar at -4.5 cells/mm(3)/year (P = .68) after adjustment for sex, HSV type 1, oral and genital herpes symptoms, immigrant status, and the interaction of immigrant status with time. However, HSV-2 seropositivity was associated with a shorter time to the first of ART initiation or CD4 <350 cells/mm(3), with an adjusted hazard ratio of 2.07 (95% confidence interval, 1.28-3.33).
  
  
  CONCLUSIONS
  HSV-2 coinfection was not associated with the rate of CD4 count decline during ART-untreated HIV infection, but was associated with an earlier combined endpoint of ART initiation or CD4 <350 cells/mm(3). Attenuating effects of acyclovir on HIV disease progression observed in recent clinical trials may result from direct anti-HIV activity rather than indirect benefits from HSV-2 suppression.
authors.affiliation: St Michael’s Hospital, Division of Infectious Diseases, 30 Bond St, 4CC Rm 4-179, Toronto, ON M5B 1W8, Canada. darrell.tan@gmail.com
authors.forename: Darrell H S
authors.initials: DH
authors.lastname: Tan
authors.forename: Janet M
authors.initials: JM
authors.lastname: Raboud
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.forename: Jason
authors.initials: J
authors.lastname: Brunetta
authors.forename: Charu
authors.initials: C
authors.lastname: Kaushic
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.forename: Edward
authors.initials: E
authors.lastname: Lee
authors.forename: Jonathan
authors.initials: J
authors.lastname: Luetkehoelter
authors.forename: Anita
authors.initials: A
authors.lastname: Rachlis
authors.forename: Fiona
authors.initials: F
authors.lastname: Smaill
authors.forename: Marek
authors.initials: M
authors.lastname: Smieja
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Walmsley
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060085:Coinfection / Q000276:immunology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male
keywords: CD4 count; HIV; cohort study; disease progression; herpes simplex virus