Hormonal contraception and the risk of HIV acquisition
ABSTRACT Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known.
To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections.
This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18-35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases).
HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69-1.42] nor DMPA (HR, 1.25; 95% CI, 0.89-1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39-5.82) and DMPA (HR, 3.97; 95% CI, 1.98-8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group.
No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.
Full-textDOI: · Available from: David D Celentano, May 30, 2015
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ABSTRACT: 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.Sex Transm Dis 03/2015; 42(3):143-152. DOI:10.1097/OLQ.0000000000000245 · 2.75 Impact Factor
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ABSTRACT: Does medroxyprogesterone acetate (MPA) impair human dendritic cell (DC) activation and function? In vitro MPA treatment suppressed expression of CD40 and CD80 by human primary DCs responding to Toll-like receptor 3 (TLR3) agonist stimulation (i.e. DC activation). Moreover, this MPA-mediated decrease in CD40 expression impaired DC capacity to stimulate T cell proliferation (i.e. DC function). MPA is the active molecule in Depo-Provera(®) (DMPA), a commonly used injectable hormonal contraceptive (HC). Although DMPA treatment of mice prior to viral mucosal tissue infection impaired the capacity of DCs to up-regulate CD40 and CD80 and prime virus-specific T cell proliferation, neither DC activation marker expression nor the ability of DCs to promote T cell proliferation were affected by in vitro progesterone treatment of human DCs generated from peripheral blood monocytes. This cross-sectional study examined MPA-mediated effects on the activation and function of human primary untouched peripheral blood DCs. Human DCs isolated from peripheral blood mononuclear cells by negative immunomagnetic selection were incubated for 24 h with various concentrations of MPA. After an additional 24 h incubation with the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C), flow cytometry was used to evaluate DC phenotype (i.e. expression of CD40, CD80, CD86, and HLA-DR). In separate experiments, primary untouched human DCs were sequentially MPA-treated, poly I:C-activated, and incubated for 7 days with fluorescently labeled naïve allogeneic T cells. Flow cytometry was then used to quantify allogeneic T cell proliferation. Several pharmacologically relevant concentrations of MPA dramatically reduced CD40 and CD80 expression in human primary DCs responding to the immunostimulant poly I:C. In addition, MPA-treated DCs displayed a reduced capacity to promote allogeneic CD4(+) and CD8(+) T cell proliferation. In other DC: T cell co-cultures, the addition of antibody blocking the CD40-CD154 (CD40L) interaction mirrored the decreased T cell proliferation produced by MPA treatment, while addition of recombinant soluble CD154 restored the capacity of MPA-treated DCs to induce T cell proliferation to levels produced by non-MPA-treated controls. While our results newly reveal that pharmacologically relevant MPA concentrations suppress human DC function in vitro, additional research is needed to learn if DMPA similarly inhibits DC maturation and function in the human female genital tract. Identification of a mechanism by which MPA impairs human DC activation and function increases the biological plausibility for the relationships currently suspected between DMPA use and enhanced susceptibility to genital tract infection. Funding provided by the NIH (grant R01HD072663) and The Ohio State University College of Medicine. The authors have no conﬂicts of interest to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: email@example.com.Human Reproduction 03/2015; 30(5). DOI:10.1093/humrep/dev035 · 4.59 Impact Factor
Article: Hormonal contraception and HIV[Show abstract] [Hide abstract]
ABSTRACT: Objective: To examine different scenarios through which confounding by condom use may lead to inaccurate conclusions about the effect of hormonal contraception on HIV acquisition in women. Design and methods: Scenario analyses were conducted to evaluate the impact of coarse adjustment for condom use and condom misreporting on adjusted relative risk estimates for HIV acquisition in injectable hormonal contraception (IHC) users vs. nonusers. Results: Analyses crudely accounting for condom use through a binary variable result in biased hormonal contraception-related risk estimates if condoms are used during follow-up periods in which any unprotected sex is reported and condom use differs by hormonal contraception use. We found that over-reporting of condom use is plausible in at least one recent study, as demonstrated by high pregnancy rates given, reported IHC and condom use. Over-reporting of condom use also biases estimates, typically leading to underestimation of IHC-related risk if over-reporting is the same among IHC and non-hormonal contraception users, and overestimation of IHC-related risk if condom misreporting is differential by IHC use. The impact of misreported condom use is most pronounced in study populations with high condom uptake. Conclusions: Discrepant findings in hormonal contraception–HIV-related research may result from inadequate measurement or adjustment for confounding by condom use. Future studies should precisely account for condom use in statistical analyses. Studies should aim to quantify the degree of condom use misreporting, by comparing reported condom use to pregnancy, HIV or other sexually transmitted infection rates, and if possible, testing stored genital swabs for prostate-specific antigen or Y chromosome.AIDS 01/2013; 27:S45-S53. DOI:10.1097/QAD.0000000000000037 · 6.56 Impact Factor