Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study.

John Bradley,Estelle Piwowar-Manning,Alicia Young,Richard J Hayes,Helen Ayles,Peter Bock,Justin Bwalya,Sian Floyd,Nomtha Bell-Mandla,Sarah Fidler,Oliver Laeyendecker

doi:10.1093/infdis/jiy178

Abstract

Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels. The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approximately 2000 adults (age range, 18-44 years) was selected randomly from each community. Baseline data on sociodemographic characteristics, behavior, and HIV/HSV2 serologic findings were used to examine the association between HIV and HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence. A total of 38691 adults participated. HSV2 prevalence among women and men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was 8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76 cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31] among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level, there was a strong linear relationship between HIV and HSV2 prevalence (ρ = 0.92; P < .001). There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention.

Highlights

Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, mechanisms are not fully understood
A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders
There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission

Summary

Methods

The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. HIV and HSV2 status were determined by testing blood samples collected from consenting survey participants. Samples that had reactive results of in-country analysis were tested with a second fourth-generation assay (GS HIV Combo Assay, Bio-Rad Laboratories, Redmond, WA). For HSV2 status, blood samples underwent in-country analysis by the Kalon HSV2 immunoglobulin G enzyme-linked immunosorbent assay (ELISA; Kalon Biological, United Kingdom), where the in-country laboratories’ performance was validated by the HPTN laboratory core [26]. We performed logistic regression analysis to explore risk factors for HSV2 infection at the individual level, stratified by sex, with adjustment for age group and study community. We examined the association between HSV2 and HIV infection at the individual level, adjusting for age group, sex, study community, and all other variables that were confounding factors for this association

Results

Discussion

Conclusion