Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis

Abstract

SummaryBackgroundHIV and herpes simplex virus type 2 (HSV-2) infections cause a substantial global disease burden and are epidemiologically correlated. Two previous systematic reviews of the association between HSV-2 and HIV found evidence that HSV-2 infection increases the risk of HIV acquisition, but these reviews are now more than a decade old.MethodsFor this systematic review and meta-analysis, we searched PubMed, MEDLINE, and Embase (from Jan 1, 2003, to May 25, 2017) to identify studies investigating the risk of HIV acquisition after exposure to HSV-2 infection, either at baseline (prevalent HSV-2 infection) or during follow-up (incident HSV-2 infection). Studies were included if they were a cohort study, controlled trial, or case-control study (including case-control studies nested within a cohort study or clinical trial); if they assessed the effect of pre-existing HSV-2 infection on HIV acquisition; and if they determined the HSV-2 infection status of study participants with a type-specific assay. We calculated pooled random-effect estimates of the association between prevalent or incident HSV-2 infection and HIV seroconversion. We also extended previous investigations through detailed meta-regression and subgroup analyses. In particular, we investigated the effect of sex and risk group (general population vs higher-risk populations) on the relative risk (RR) of HIV acquisition after prevalent or incident HSV-2 infection. Higher-risk populations included female sex workers and their clients, men who have sex with men, serodiscordant couples, and attendees of sexually transmitted infection clinics.FindingsWe identified 57 longitudinal studies exploring the association between HSV-2 and HIV. HIV acquisition was almost tripled in the presence of prevalent HSV-2 infection among general populations (adjusted RR 2·7, 95% CI 2·2–3·4; number of estimates [Ne]=22) and was roughly doubled among higher-risk populations (1·7, 1·4–2·1; Ne=25). Incident HSV-2 infection in general populations was associated with the highest risk of acquisition of HIV (4·7, 2·2–10·1; Ne=6). Adjustment for confounders at the study level was often incomplete but did not significantly affect the results. We found moderate heterogeneity across study estimates, which was explained by risk group, world region, and HSV-2 exposure type (prevalent vs incident).InterpretationWe found evidence that HSV-2 infection increases the risk of HIV acquisition. This finding has important implications for management of individuals diagnosed with HSV-2 infection, particularly for those who are newly infected. Interventions targeting HSV-2, such as new HSV vaccines, have the potential for additional benefit against HIV, which could be particularly powerful in regions with a high incidence of co-infection.FundingWorld Health Organization.

Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study

“…Many previous studies have documented the strong association between these 2 infections at the individual level, and this finding has been remarkably consistent across different studies and settings [4, 28]. In cross-sectional studies (including the current analysis), the direction of causality cannot be definitively established, and some or all of the association might be explained by an effect of HIV on the acquisition of HSV2 infection.…”

Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta‐analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status

“…As with other systematic and meta‐analytic reviews of longitudinal studies of STI and HIV interactions, there are some limitations to our reviews that may affect our results in either direction . HPV and HIV are both STIs associated with similar sexual risk factors, which may lead to overestimation of the magnitude of STI and HIV associations.…”

“…Whilst we found that the magnitude of the association was similar by timing of HPV infection (incident, prevalent or cleared infection), differing types and density of immunological cells in the genital area could in theory translate into varying risk of HIV acquisition over the course of HPV infection and warrants further investigation. A recent systematic review and meta‐analysis of 57 studies found higher risk of HIV acquisition in those with incident HSV‐2 infection (compared to those without HSV‐2 infection) than was found for prevalent HSV‐2 infection . The interactions between HIV and HPV could be analogous to the interactions between HIV and HSV‐2 in terms of some similarity of biological mechanisms.…”

Epidemiology of Alcohol Misuse and Illicit Drug Use Among Young People Aged 15–24 Years in Fishing Communities in Uganda

“…Evidence suggests a direct and reciprocal biological interaction between HIV and HSV2 [46]. Additionally, HIV and HSV2 are associated with similar risk factors [age, sex, partner change, condom use and male circumcision) [46]. Thus, HSV2 may be considered a proxy measure for risky sexual behaviour.…”