Rebecca G Nowak1, Tobias A Liska2, Søren M Bentzen3, Esther Kim4, Tsungai Chipato5, Robert A Salata6, David D Celentano7, Charles S Morrison8, Patti E Gravitt3. 1. Division of Epidemiology and Prevention, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD. 2. Nathan Schnaper Internship Program in Translational Cancer Research, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD. 3. Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD. 4. Beth Israel Lahey Health Beverly Hospital, Beverly MA. 5. Department of Obstetrics and Gynecology, University of Zimbabwe, Harare, Zimbabwe. 6. Department of Medicine, Case Western Reserve University, Cleveland, OH. 7. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;and. 8. Behavioral, Epidemiologic and Clinical Sciences, Durham, NC.
Abstract
BACKGROUND: Herpes simplex virus type-2 (HSV-2) seropositive persons have a 3- to 5-fold higher risk of acquiring HIV, possibly because of HSV-2-induced inflammation and recruitment of susceptible immune cells to exposure sites. We hypothesized that cervical HSV-2 activation (ie, 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. Up to 5 cervical swabs bracketing first polymerase chain reaction detection of HIV DNA (the index visit) were selected (t-6months, t-3months, tindex, t+3months, t+6months). Women with HSV-2 immunoglobulin G+ before tindex were polymerase chain reaction 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 (CIs) at each visit. RESULTS: Of 387 HSV-2 seropositive women, most had prevalent as compared with 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 to 8.8; tindex aOR, 2.6; 95% CI, 1.1 to 6.5; t+3months aOR, 2.6; 95% CI, 1.0 to 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 to 133.9). CONCLUSIONS: HSV-2 shedding appeared synergistic with HIV acquisition followed by presentation of ulcers. Evaluating all sexually transmitted infections rather than HSV-2 alone may clarify the relationship between inflammation and HIV acquisition.
BACKGROUND: Herpes simplex virus type-2 (HSV-2) seropositive persons have a 3- to 5-fold higher risk of acquiring HIV, possibly because of HSV-2-induced inflammation and recruitment of susceptible immune cells to exposure sites. We hypothesized that cervical HSV-2 activation (ie, 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. Up to 5 cervical swabs bracketing first polymerase chain reaction detection of HIV DNA (the index visit) were selected (t-6months, t-3months, tindex, t+3months, t+6months). Women with HSV-2 immunoglobulin G+ before tindex were polymerase chain reaction 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 (CIs) at each visit. RESULTS: Of 387 HSV-2 seropositive women, most had prevalent as compared with 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 to 8.8; tindex aOR, 2.6; 95% CI, 1.1 to 6.5; t+3months aOR, 2.6; 95% CI, 1.0 to 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 to 133.9). CONCLUSIONS: HSV-2 shedding appeared synergistic with HIV acquisition followed by presentation of ulcers. Evaluating all sexually transmitted infections rather than HSV-2 alone may clarify the relationship between inflammation and HIV acquisition.
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