Abstract

WEAC0201 - Oral Abstract Session

Association between STI/RTI infections, altered cervical innate immunity and HIV-1 seroconversion among hormonal contraceptive users

Presented by Raina Fichorova (United States).

R. Fichorova¹, C. Morrison², G. Doncel³, P.-L. Chen², C. Kwok², T. Chipato⁴, R. Salata⁵, C. Mauck<sup>6

1</sup>Brigham and Women's Hospital, Harvard Medical School, Boston, United States, ²Family Health International (FHI 360), Durham, United States, ³CONRAD, Eastern Virginia Medical School, Norfolk, United States, ⁴University of Zimbabwe, Harare, Zimbabwe, ⁵Case Western Reserve University, Cleveland, United States, ⁶CONRAD, Eastern Virginia Medical School, Arlington, United States

Background: Hormonal contraceptives (HC) have been associated with risk of HIV-1 seroconversion in women and their partners. We examined the association between injectable HC (DMPA), combined oral contraceptives (COC), and no hormonal contraceptive use (NH) with genital tract mucosal immunity biomarkers in women with STI/RTI who did or did not become HIV infected.
Methods: Biomarkers were quantified in cervical swabs from 832 HIV-uninfected reproductive-aged Ugandan and Zimbabwean women with documented HC use, HIV/STI behavioral risk factors, STI/RTI signs and symptoms, and were correlated with HIV-1 seroconversion at next visit. C. trachomatis (CT) and N. gonorrhoeae (NG) were diagnosed by PCR, genital herpes by HSV-2 antibody ELISA, BV by Nugent score, and candida by wet mount. Multivariable generalized linear models utilizing Box-Cox power transformation examined associations between levels of biomarkers and risk factors for HIV infection (STIs including signs and symptoms, HC use). Odds ratios with Breslow-Day test for homogeneity described the risk of having top quartile concentrations of biomarkers in STI/RTI+ versus negative women across HC groups.
Results: Women who had both signs and symptoms of STI/RTI had higher beta-defensin (BD)2 and lower SLPI levels in cervical secretions compared to STI-free women. Both of these changes were associated with HIV seroconversion (occurring among 24% of women at the next visit). Among women with BV, odds of top quartile BD2 levels were higher in the OC and DMPA users than in the NH group. When compared to NH, DMPA use was associated with lower levels of the anti-inflammatory regulator IL-1RA overall and, in women with intermediary vaginal microflora, HSV-2 and NG, with significantly lower odds of top quartile IL-1RA concentrations.
Conclusions: OC and DMPA differentially modulate levels of cervical protective immune mediators, altering responses to STI/RTIs, and providing insight into possible biological mechanisms for higher risk of HIV acquisition.