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

Background:

Biological and epidemiological evidence suggest that herpes simplex virus type 2 (HSV-2) elevates HIV acquisition and transmission risks. We improved previous estimates of the contribution of HSV-2 to HIV infections by using a dynamic transmission model.

Setting:

World Health Organization regions.

Methods:

We developed a mathematical model of HSV-2/HIV transmission among 15- to 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 10 years [the transmission population-attributable fraction (tPAF)] under 3 additive scenarios, assuming: (1) HSV-2 increases only HIV acquisition risk (conservative); (2) HSV-2 also increases HIV transmission risk (liberal); and (3) HIV or antiretroviral therapy (ART) also modifies HSV-2 transmission risk, and HSV-2 decreases ART effect on HIV transmission risk (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 approximately 50% and 1.3- to 2.4-fold higher for the liberal or fully liberal scenario than the conservative scenario across regions.

Conclusion:

HSV-2 may have contributed to at least 37% of incident HIV infections in the past 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.