Herpes Simplex Virus Type-2 shedding and genital ulcers during early HIV in Zimbabwean women.

BACKGROUND Herpes Simplex Virus Type-2 (HSV-2) seropositive persons have a 3-5 fold higher risk of acquiring HIV, possibly due to HSV-2 induced inflammation and recruitment of susceptible immune cells to exposure sites. We hypothesized cervical HSV-2 activation (i.e., viral DNA shedding and/or ulcers) preceded HIV acquisition in the Hormonal Contraception and HIV cohort. METHODS Zimbabwean women who acquired HIV were matched to HIV-negative women on visit, age, and bacterial sexually transmitted infections (STIs). Up to 5 cervical swabs bracketing first PCR detection of HIV DNA, the index visit, were selected (t-6months, t-3months, tindex, t+3months, t+6months). Women with HSV-2 IgG+ before tindex were PCR-tested for viral shedding. Self-reported and clinician-diagnosed ulcers were documented. Multivariable logistic regression, accounting for matching, estimated adjusted odds ratios [aOR] and 95% confidence intervals [CI] at each visit. RESULTS Of 387 HSV-2 seropositive women, most had prevalent as compared to incident HSV-2 (91% vs. 9%, respectively). HSV-2 viral shedding was more common among HIV seroconverters than HIV-negative women (26% vs. 14%, p<0.01). Shedding occurred around HIV acquisition (t-3months aOR: 2.7, 95% CI: 0.8-8.8; tindex aOR: 2.6, 95% CI: 1.1-6.5; t+3months aOR: 2.6, 95% CI: 1.0-6.6). Genital ulcers were reported more often among HIV seroconverters than HIV-negative women (13% vs. 7%, p=0.06) and detection was after HIV acquisition (t+6months aOR: 14.5, 95% CI: 1.6-133.9). CONCLUSIONS HSV-2 shedding appeared synergistic with HIV acquisition followed by presentation of ulcers. Evaluating all STIs rather than HSV-2 alone may clarify the relationship between inflammation and HIV acquisition.