What is the burden of heterosexually-acquired HIV due to HSV-2? Global and regional model-based estimates of the proportion and number of HIV infections attributable to HSV-2 infection

Abstract

Background: Biological and epidemiological evidence suggest that herpes simplex virus type 2 (HSV-2) elevates HIV acquisition and transmission risk. We improved previous estimates of the contribution of HSV-2 to HIV infections by using a dynamic-transmission model. Setting: WHO regions. Methods: We developed a mathematical model of HSV-2/HIV transmission among 15-49-year-old heterosexual, non-drug-injecting populations, calibrated using region-specific demographic and HSV-2/HIV epidemiological data. We derived global and regional estimates of the contribution of HSV-2 to HIV infection over ten years (the transmission population-attributable fraction, tPAF) under three additive scenarios, assuming: (1) HSV-2 only increases HIV acquisition (“conservative”); (2) HSV-2 also increases HIV transmission (“liberal”); (3) HIV/ART (antiretroviral therapy) also modifies HSV-2 transmission and HSV-2 decreases ART effect on HIV transmission ("fully liberal”). Results: Under the conservative scenario, the predicted tPAF was 37.3% (95% uncertainty interval 33.4-43.2%) and an estimated 5.6 (4.5-7.0) million incident heterosexual HIV infections were due to HSV-2 globally over 2009-2018. The contribution of HSV-2 to HIV infections was largest for the African region (tPAF=42.6% (38.0-51.2%)), and lowest for the European region (tPAF=11.2% (7.9-13.8%)). The tPAF was higher among female sex-workers, their clients, and older populations, reflecting their higher HSV-2 prevalence. The tPAF was ∼50% and 1.3-2.4-fold higher for the liberal/fully liberal than the conservative scenario across regions. Conclusion: HSV-2 may have contributed to at least 37% of incident HIV infections in the last decade worldwide, and even more in Africa, and may continue to do so despite increased ART access unless future improved HSV-2 control measures, such as vaccines, become available.