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Open Access Highly Accessed Research article

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

Darrell Hoi-San Tan1234*, Kellie Murphy45, Prakesh Shah46 and Sharon Lynn Walmsley234

Author Affiliations

1 Division of Infectious Diseases, St. Michael’s Hospital, 30 Bond St. 4CC – Room 4-179, Toronto, ON M5B 1W8, Canada

2 Division of Infectious Diseases, University Health Network, 585 University Ave. 13-N, Toronto, ON M5G 2N2, Canada

3 Division of Infectious Diseases, University of Toronto, 200 Elizabeth St, Toronto, ON M5G 2C4, Canada

4 Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College St., Suite 425, Toronto, ON M5T 3M6, Canada

5 Department of Maternal Fetal Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada

6 Department of Pediatrics, University of Toronto, 600 University Ave., Room 775-A, Toronto, ON M5G 1X5, Canada

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BMC Infectious Diseases 2013, 13:502  doi:10.1186/1471-2334-13-502

Published: 28 October 2013

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/mm3). 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.

Keywords:
Herpes simplex virus; Human immunodeficiency virus; Disease progression; Viral load; CD4 count; Seropositivity; Systematic review