Article

Hormonal contraception and the risk of HIV acquisition

Johns Hopkins University, Baltimore, Maryland, United States
AIDS (Impact Factor: 6.56). 02/2007; 21(1):85-95. DOI: 10.1097/QAD.0b013e3280117c8b
Source: PubMed

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.

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    • "Objections however were quickly raised regarding the reliability of this data, including its low biological plausibility and the high likelihood that results had been confounded by unmeasured differences in condom usage and frequency of unprotected intercourse between the HC users and non-users (Gray, 2012; Hubacher, 2012; Shelton, 2012; van Leeuewn and de Vries, 2012). Moreover, discordant results between other studies exploring links between DMPA and HIV acquisition implied that uncontrolled differences among HC users and non-users were similarly responsible for systematic study biases (Baeten et al., 2007; Kleinschmidt et al., 2007; Morrison et al., 2007, 2010, 2014; Myer et al., 2007; Kumwenda et al., 2008). The difficulties eradicating systemic bias from such studies, combined with their sizable public health implications, were impetus for developing complementary approaches that more clearly define the connections between HC and sexually transmissible infection (STI) acquisition. "
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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: journals.permissions@oup.com.
    Human Reproduction 03/2015; 30(5). DOI:10.1093/humrep/dev035 · 4.59 Impact Factor
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    • "The other studies reported non-significant estimates (ranging from adjusted incidence rate ratio [adjIRR] 0.66, 95% CI0.09-4.78 to adjHR 1.80, 95% CI0.47-5.66).[41] [42] [53] [57] [59] [60] [62] [64] No substantial differences were observed between combined oral contraceptives (COCs) and progestin-only pills (POPs) in the one study that disaggregated these methods.[62] "
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    ABSTRACT: Whether use of various types of hormonal contraception (HC) affect risk of HIV acquisition is a critical question for women’s health. For this systematic review, we identified 22 studies published by January 15, 2014 which met inclusion criteria; we classified thirteen studies as having severe methodological limitations, and nine studies as “informative but with important limitations”. Overall, data do not support an association between use of oral contraceptives and increased risk of HIV acquisition. Uncertainty persists regarding whether an association exists between depot-medroxyprogesterone acetate (DMPA) use and risk of HIV acquisition. Most studies suggested no significantly increased HIV risk with norethisterone enanthate (NET-EN) use, but when assessed in the same study, point estimates for NET-EN tended to be larger than for DMPA, though 95% confidence intervals overlapped substantially. No data have suggested significantly increased risk of HIV acquisition with use of implants, though data were limited. No data are available on the relationship between use of contraceptive patches, rings, or hormonal intrauterine devices and risk of HIV acquisition. Women choosing progestin-only injectable contraceptives such as DMPA or NET-EN should be informed of the current uncertainty regarding whether use of these methods increases risk of HIV acquisition, and like all women at risk of HIV, should be empowered to access and use condoms and other HIV preventative measures. Programs, practitioners, and women urgently need guidance on how to maximize health with respect to avoiding both unintended pregnancy and HIV given inconclusive or limited data for certain HC methods.
    Contraception 10/2014; 90(4). DOI:10.1016/j.contraception.2014.07.009 · 2.93 Impact Factor
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    • "Most research on family planning and HIV has not focused on providers but rather on the physiologic effects of hormonal contraception and antiretroviral therapies [39–41] and on the unmet need for contraception and fertility desires among HIV-positive clients [1, 42–45]. We found that knowledge about the safety and appropriate use of family planning methods among HIV-positive individuals was limited as it has also been found in Uganda [26]. "
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    ABSTRACT: Objective. To inform an intervention integrating family planning into HIV care, family planning (FP) knowledge, attitudes and practices, and perspectives on integrating FP into HIV care were assessed among healthcare providers in Nyanza Province, Kenya. Methods. Thirty-one mixed-method, structured interviews were conducted among a purposive sample of healthcare workers (HCWs) from 13 government HIV care facilities in Nyanza Province. Structured questions and case scenarios assessed contraceptive knowledge, training, and FP provision experience. Open-ended questions explored perspectives on integration. Data were analyzed descriptively and qualitatively. Results. Of the 31 HCWs interviewed, 45% reported previous FP training. Few providers thought long-acting methods were safe for HIV-positive women (19% viewed depot medroxyprogesterone acetate as safe and 36% viewed implants and intrauterine contraceptives as safe); fewer felt comfortable recommending them to HIV-positive women. Overall, providers supported HIV and family planning integration, yet several potential barriers were identified including misunderstandings about contraceptive safety, gendered power differentials relating to fertility decisions, staff shortages, lack of FP training, and contraceptive shortages. Conclusions. These findings suggest the importance of considering issues such as patient flow, provider burden, commodity supply, gender and cultural issues affecting FP use, and provider training in FP/HIV when designing integrated FP/HIV services in high HIV prevalence areas.
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