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. Mauck6
1Brigham 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
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.
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.
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