title: Herpes simplex virus type 2 and HIV disease progression: a systematic review of observational studies.
abstract: BACKGROUND
  Herpes simplex virus type 2 (HSV-2) is a common co-infection among HIV-infected adults that is hypothesized to accelerate HIV disease progression.
  
  
  METHODS
  We searched Medline, EMBASE, relevant conference proceedings (2006-12) and bibliographies of identified studies without language restriction for cohort studies examining the impact of HSV-2 on highly active antiretroviral therapy-untreated HIV disease in adults. The exposure of interest was HSV-2 seropositivity or clinical/laboratory markers of HSV-2 activity. The primary outcome was HIV disease progression, defined as antiretroviral initiation, development of AIDS/opportunistic infection, or progression to CD4 count thresholds (≤ 200 or ≤ 350 cells/mm(3)). Secondary outcomes included HIV plasma viral load and CD4 count.
  
  
  RESULTS
  Seven studies were included. No definitive relationship was observed between HSV-2 seropositivity and time to antiretroviral initiation (n=2 studies), CD4 ≤ 350 (n=1), CD4 ≤ 200 (n=1), death (n=1), viral load (n=6) or CD4 count (n=3). Although two studies each observed trends towards accelerated progression to clinical AIDS/opportunistic infection in HSV-2 seropositives, with pooled unadjusted hazard ratio=1.85 (95% CI=1.12,3.06; I2=2%), most OIs observed in the study for which data were available can occur at high CD4 counts and may not represent HIV progression. In contrast, a single study HSV-2 disease activity found that the presence of genital HSV-2 DNA was associated with a 0.4 log copies/mL increase in HIV viral load.
  
  
  CONCLUSIONS
  Despite an observation that HSV-2 activity is associated with increased HIV viral load, definitive evidence linking HSV-2 seropositivity to accelerated HIV disease progression is lacking. The attenuating effects of acyclovir on HIV disease progression observed in recent trials may result both from direct anti-HIV activity as well as from indirect benefits of HSV-2 suppression.
authors.affiliation: Division of Infectious Diseases, St, Michael's Hospital, 30 Bond St, 4CC - Room 4-179, Toronto, ON M5B 1W8, Canada. darrell.tan@gmail.com.
authors.forename: Darrell Hoi-San
authors.initials: DH
authors.lastname: Tan
authors.forename: Kellie
authors.initials: K
authors.lastname: Murphy
authors.forename: Prakesh
authors.initials: P
authors.lastname: Shah
authors.forename: Sharon Lynn
authors.initials: SL
authors.lastname: Walmsley
mesh_terms: D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000097:blood / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D015658:HIV Infections / Q000097:blood / Q000473:pathology / Q000821:virology*; D006558:Herpes Genitalis / Q000097:blood / Q000473:pathology / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000302:isolation & purification*; D006801:Humans; D019562:Viral Load