Several co-factors for HPV oncogenesis have been proposed, including co-infection with HSV-2. We assessed the relationship between HSV-2 infection and HPV-related outcomes in quadrivalent HPV-vaccinated (qHPV) women living with HIV (WLWH). In this multi-site study of immunogenicity and efficacy of the qHPV vaccine in WLWH, visits took place at months -3, 0, 2, 6, 12, 18, 24, and annually thereafter. Participants provided clinical data and cervico-vaginal swabs for HPV DNA detection; baseline serum was tested for HSV-2 type-specific antibodies. We used non-parametric statistics to compare HPV-related outcomes by HSV-2 serostatus and use of anti-HSV medication. 151 baseline serum samples underwent HSV-2 testing. At baseline, median age was 39 years, median CD4 count was 500cells/mm3, and 70% had an HIV viral load of <50copies/mL. Baseline HSV-2 seroprevalence was 76.2%. HSV-2 seropositivity was associated with increased age (p = 0.006). Controlling for age and median CD4 count, HSV-2 seropositivity was not associated with HPV incidence, persistence, and precancerous lesions. The use of anti-HSV medications was associated with higher odds of HSIL cytology (OR = 3.35, 95% CI = 1.03,11.26) and a greater number of HPV types detected (OR = 1.18, 95% CI = 1.00,1.39). Results were similar in sensitivity analyses using an index value of 3.5. The presence of HSV lesions during the study was not associated with HPV outcomes. HSV-2 seropositivity was common in this cohort of WLWH in Canada but was not associated with multiple measures of HPV incidence, persistence, and precancerous lesions. However, the use of anti-HSV medications was associated with HSIL cytology and number of HPV types detected.
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