Associations of Hormonal Contraceptive Use with Measures of HIV Disease Progression & Antiretroviral Therapy Effectiveness

OBJECTIVE:

To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness.

STUDY DESIGN:

A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350cells/mm(3), ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method.

RESULTS:

During a total of 5233months follow-up among participants not using ART with enrollment CD4 ≥350cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods.

CONCLUSION:

Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.

IMPLICATIONS:

Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.

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By:   Whiteman MK1, Jeng G2, Samarina A3, Akatova N3, Martirosyan M3, Kissin DM2, Curtis KM2, Marchbanks PA2, Hillis SD2, Mandel MG2, Jamieson DJ2.

• 1Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: acq5@cdc.gov.
• 2Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA.
• 3St. Petersburg AIDS Center, St. Petersburg, Russia.
• Contraception. 2016 Jan;93(1):17-24. doi: 10.1016/j.contraception.2015.07.003. Epub 2015 Jul 18.
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The Impact of Hormonal Contraception and Pregnancy on Sexually Transmitted Infections and on Cervicovaginal Microbiota in African Sex Workers

The observed association between Depo-Provera injectable use and increased HIV acquisition may be caused by hormone-induced increased susceptibility to other sexually transmitted infections (STIs) or changes in the cervicovaginal microbiota (VMB), accompanied by genital immune activation and/or mucosal remodeling.

Rwandan female sex workers (n = 800) were interviewed about contraceptive use and sexual behavior and were tested for STIs, bacterial vaginosis by Nugent score and pregnancy, at baseline. A subset of 397 HIV-negative, nonpregnant women were interviewed and tested again at regular intervals for 2 years. The VMB of a subset of 174 women was characterized by phylogenetic microarray. Outcomes of STI and VMB were compared between women with hormonal exposures (reporting oral contraceptive or injectable use, or testing positive for pregnancy) and controls (not reporting hormonal contraception and not pregnant).

Oral contraceptive use was associated with increased human papillomavirus prevalence (adjusted odds ratio [aOR], 3.10; 1.21-7.94) and Chlamydia trachomatis incidence (aOR, 6.13; 1.58-23.80), injectable use with increased herpes simplex virus-2 prevalence (aOR, 2.13; 1.26-3.59) and pregnancy with lower HIV prevalence (aOR, 0.45; 0.22-0.92) but higher candidiasis incidence (aOR, 2.14; 1.12-4.09). Hormonal status was not associated with Nugent score category or phylogenetic VMB clustering, but oral contraceptive users had lower semiquantitative vaginal abundance of Prevotella, Sneathia/Leptotrichia amnionii, and Mycoplasma species.

Oral contraceptive and injectable use were associated with several STIs but not with VMB composition. The increased herpes simplex virus-2 prevalence among injectable users might explain the potentially higher HIV risk in these women, but more research is needed to confirm these results and elucidate biological mechanisms.

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By: Borgdorff H1, Verwijs MC, Wit FW, Tsivtsivadze E, Ndayisaba GF, Verhelst R, Schuren FH, van de Wijgert JH.

• 1From the *Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center, Amsterdam, the Netherlands; †Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; ‡TNO Microbiology & Systems Biology, Zeist, the Netherlands; §Rinda Ubuzima, Kigali, Rwanda; and ¶International Center for Reproductive Health, Ghent University, Ghent, Belgium. 

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