Global population-level association between herpes simplex virus 2 prevalence and HIV prevalence

BACKGROUND: Our objective was to assess the population-level association between herpes simplex virus 2 (HSV-2) and HIV prevalence. METHODS: Reports of HSV-2 and HIV prevalence were systematically reviewed and synthesized following PRISMA guidelines. Spearman rank correlation ([Image: see text]) was used to assess correlations. Risk ratios (RR(HSV-2/HIV)) and odds ratios (OR(HSV-2/HIV)) were used to assess HSV-2/HIV epidemiologic overlap. DerSimonian–Laird random-effects meta-analyses were conducted. RESULTS: In total, 939 matched HSV-2/HIV prevalence measures were identified from 77 countries. HSV-2 prevalence was consistently higher than HIV prevalence. Strong HSV-2/HIV prevalence association was found for all data ([Image: see text] = 0.6, P < 0.001), all data excluding people who inject drugs (PWID) and children ([Image: see text] = 0.7, P < 0.001), female sex workers ([Image: see text] = 0.5, P < 0.001), and MSM ([Image: see text] = 0.7, P < 0.001). No association was found for PWID ([Image: see text] = 0.2, P = 0.222) and children ([Image: see text] = 0.3, P = 0.082). A threshold effect was apparent where HIV prevalence was limited at HSV-2 prevalence less than 20%, but grew steadily with HSV-2 prevalence for HSV-2 prevalence greater than 20%. The overall pooled mean RR(HSV-2/HIV) was 5.0 (95% CI 4.7–5.3) and OR(HSV-2/HIV) was 9.0 (95% CI 8.4–9.7). The RR(HSV-2/HIV) and OR(HSV-2/HIV) showed similar patterns that conveyed inferences about HSV-2 and HIV epidemiology. CONCLUSION: HSV-2 and HIV prevalence are strongly associated. HSV-2 prevalence can be used as a proxy ‘biomarker’ of HIV epidemic potential, acting as a ‘temperature scale’ of the intensity of sexual risk behavior that drive HIV transmission. HSV-2 prevalence can be used to identify populations and/or sexual networks at high-risk of future HIV expansion, and help prioritization, optimization, and resource allocation of cost-effective prevention interventions.