Background: Many studies have identified associations between HIV and Herpes simplex virus type-2 (HSV2), the commonest viral sexually transmitted infection, although the exact role of HSV2 as a cofactor in HIV transmission is unknown. A large community-randomised trial of an HIV preventive intervention afforded an opportunity to re-examine this association at individual and community levels.
Methods: The HPTN071(PopART) trial is measuring the impact of a combination prevention intervention on HIV incidence at population-level in 21 urban communities in Zambia and South Africa. To measure impact, a population-cohort of approximately 2,000 adults aged 18-44 was selected randomly from each community. Baseline data were collected on socio-demographic characteristics and sexual behaviour, and serological tests performed for HIV and HSV2 infection. Logistic regression was used to examine the association between HIV and HSV2 after adjustment for confounders. At community-level, HIV prevalence was plotted against HSV2 prevalence.
Results: 38,691 adults were enrolled in the cohort. Overall HSV2 prevalence in men and women was 22% and 50% in Zambia, and 26% and 59% in South Africa. At individual level (Table) a six-fold higher odds of HIV was seen in HSV2-infected individuals in both sexes, even after adjustment for other risk factors including lifetime number of sex partners. At community-level there was a strong linear relationship between HIV prevalence and HSV2 infection (Figure).

 HSV2-veHSV2+veOR (adj for age, community)OR (adj for age, cty, partners, other)
Males372/7,657 (4.9%)834/2,401 (34.7%)6.28 (p<0.001)5.76 (p<0.001)
Females790/11,380 (6.9%)5652/13,305(42.5%)7.40 (p<0.001)6.38 (p<0.001)
[Association between HIV and HSV2 in 21 communities]

HIV and HSV2 prevalence in 21 communities
[HIV and HSV2 prevalence in 21 communities]

Conclusions: These data show the exquisite association between these two infections, seen at both individual and community levels. While both viruses are sexually transmitted, the associations remained strong after adjustment for measures of sexual behaviour. This association is likely due at least partly to a powerful biological cofactor effect of HSV2 on HIV acquisition. Effective control tools for HSV2 could make an important contribution to HIV prevention.

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