Strong Association Between HIV Incidence and Herpes Simplex Virus Type 2 in Zambia and South Africa: Prospective Data From the HPTN 071 (PopART) Trial

Open Forum Infect Dis. 2024 Dec 14;12(1):ofae721. doi: 10.1093/ofid/ofae721. eCollection 2025 Jan.

Abstract

Background: Herpes simplex virus type 2 (HSV2) is an important cofactor for HIV acquisition and transmission. Associations between the infections are reexamined in longitudinal data from an HIV prevention trial.

Methods: The HPTN 071 (PopART) trial evaluated a combination prevention intervention in 21 urban communities in Zambia and South Africa. HIV incidence was measured in a cohort of approximately 2000 adults (age, 18-44 years) selected randomly from each community and followed up for 36 months. Incidence of HSV2 infection was estimated, and the effects of risk factors were examined. The association between HIV incidence and HSV2 infection was examined at individual and community levels.

Results: An overall 10 539 participants were HSV2 negative at baseline and retested after 36 months. Estimated HSV2 incidence was 5.4 per 100 person-years (95% CI, 5.0-5.7) for women and 2.9 per 100 person-years (95% CI, 2.6-3.2) for men. When compared with those remaining HSV2 negative, HIV incidence was higher in those who were HSV2 positive at baseline (women: adjusted rate ratio [aRR], 3.24 [95% CI, 2.50-4.20]; men: aRR, 2.57 [95% CI, 1.60-4.11]) and even higher in those who seroconverted to HSV2 during follow-up (women: aRR, 5.94 [95% CI, 4.42-7.98]; men: aRR, 8.37 [95% CI, 5.18-13.52]). At the community level, strong associations were seen between HIV incidence and HSV2 prevalence (R 2 = 0.48, P < .001) and incidence (R 2 = 0.36, P = .004).

Conclusions: There were strong associations between HIV incidence and HSV2 prevalence and incidence at individual and community levels. HSV2 control could contribute to HIV prevention.

Keywords: HIV; HSV2; Southern Africa; cofactor; prospective.