Herpes simplex virus type 2 and HIV disease progression: a systematic review of observational studies

Darrell Hoi-San Tan,Sharon Lynn Walmsley,Kellie Murphy,Prakesh Shah

doi:10.1186/1471-2334-13-502

Abstract

BackgroundHerpes simplex virus type 2 (HSV-2) is a common co-infection among HIV-infected adults that is hypothesized to accelerate HIV disease progression.MethodsWe 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/mm3). Secondary outcomes included HIV plasma viral load and CD4 count.ResultsSeven 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.ConclusionsDespite 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.

Highlights

Herpes simplex virus type 2 (HSV-2) is a common co-infection among HIV-infected adults that is hypothesized to accelerate HIV disease progression
Study and participant criteria Cohort studies examining the impact of HSV-2 coinfection on progression of antiretroviral therapy (ART)-untreated HIV disease over ≥6 months, HIV plasma viral load, or CD4 count were considered for inclusion
A meta-analysis from the pre-HAART era suggested that >3200 mg per day of acyclovir offered a significant survival benefit [20], but it is unclear whether the improved survival was only related to eradication of herpesviruses or whether there could have been a secondary impact on HIV replication

Summary

Introduction

Herpes simplex virus type 2 (HSV-2) is a common co-infection among HIV-infected adults that is hypothesized to accelerate HIV disease progression. Herpes simplex virus type 2 (HSV-2) is a common pathogen that co-infects over half of HIV-infected adults [1], and may accelerate HIV disease by increasing plasma HIV viral load [2,3]. The leading hypothesis is that by suppressing HSV-2 activity, acyclovir reverses the adverse impact of HSV-2 co-infection on HIV disease progression. In vitro data have suggested that acyclovir may have direct anti-HIV activity [7,8], raising the possibility that anti-HIV effects may have contributed to the trial findings

Methods

Results

Discussion

Conclusion