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Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies

Freeman, Esther Ea; Weiss, Helen Aa; Glynn, Judith Ra; Cross, Pamela La; Whitworth, James Aa,b; Hayes, Richard Ja

Epidemiology and Social

Objective: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection.

Background: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women.

Design: Systematic review and meta-analysis of longitudinal studies.

Methods: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated.

Results: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9–3.9] and women (RR, 3.1; 95% CI, 1.7–5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2–2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association.

Conclusions: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.

From the aInfectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine

bWellcome Trust, London, UK.

Received 9 March, 2005

Revised 13 June, 2005

Accepted 27 July, 2005

Correspondence to E. Freeman. Harvard Medical School, Francis Weld Peabody Society, 260 Longwood Ave., Boston MA 02115, USA. E-mail:

© 2006 Lippincott Williams & Wilkins, Inc.