Injectable contraceptive may raise HIV infection risk by 40%

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The injectable progestin contraceptive depot medroxyprogesterone acetate (DMPA) may raise the risk for HIV infection by 40% in women, according to a research review.

DMPA is the major form of hormonal contraceptive used in sub-Saharan Africa, which also has the highest worldwide HIV prevalence, particularly in young women, Healio reports the researchers noted in the review. Other forms of contraception, including combined oral contraceptives containing levonorgestrel or the injectable contraceptive norethisterone enanthate, were not associated with increased HIV infection risk, they wrote.

“Medroxyprogesterone acetate (MPA) used as a highly effective three-monthly injectable contraceptive, Depo-Provera, acts differently to other progestins widely used in contraceptives,” Dr Janet P Hapgood, of the department of molecular and cell biology and the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, South Africa, is quoted in the report as saying. “Available clinical, animal, and biochemical data are broadly consistent and support the possibility that MPA increases HIV-1 acquisition by actively suppressing the immune system and weakening the protective barrier function of the female genital tract, by multiple mechanisms.”

In the review, Hapgood and colleagues wrote that individual progestins used in hormonal contraceptives have different biological effects via specific steroid receptors, and that oestrogen may exert a protective, antiviral effect. In a review of animal, cell and biochemical research on the form of progestin used in DMPA – medroxyprogesterone acetate (MPA) – a researchers found evidence that “supports a role for MPA in increasing the permeability of the female genital tract and promoting HIV uptake.”

“Geographically, areas with the highest usage of injectable contraceptives overlap with those with the highest HIV-1 prevalence,” the researchers wrote. “A recent meta-analysis of epidemiological data, involving tens of thousands of women, suggests that DMPA usage may be associated with a 40% (95% CI, 23-59) increase in risk of HIV-1 acquisition.”

The analysis revealed MPA suppresses plasmacytoid dendritic cell and T-cell function, and it suppresses select regulators of cellular and humoral systemic immunity. Additionally, researchers cited “strong clinical and experimental animal data” supporting a role for MPA in increasing the frequency of HIV viral targets in the female genital tract, as well as evidence for MPA use increasing the levels of the C-C chemokine receptor type 5 co-receptor for HIV entry.

The researchers noted that the relative contribution of different mechanisms for MPA is unknown, and further investigation is needed.

“Together the reviewed data provide a compelling case against the continuous use of Depo-Provera in areas of high HIV-1 prevalence provided other forms of safe, affordable, non-hormonal or hormonal contraceptive methods are readily available,” Hapgood said.

“Insufficient or no information is available regarding the biological mechanisms of action relevant to HIV-1 acquisition of progestins other than MPA. Further investigation is needed regarding the potential effect of other forms of hormonal contraception, including DMPA-SC, or non-hormonal contraceptives on HIV-1 acquisition. Combined evidence supports a focus on methods that avoid progestins with relatively potent glucocorticoid receptor activity, such as MPA.”

Access to effective affordable contraception for women is critical for individual and public health. A wide range of hormonal contraceptives (HCs) which differ in the composition, concentration of progestin component, frequency of dosage and method of administration, is currently available globally. However, the options are rather limited in settings with restricted economic resources that frequently overlap with areas of high HIV-1 prevalence. The predominant contraceptive used in Sub-Saharan Africa is the progestin-only three-monthly injectable depo-medroxyprogesterone acetate (DMPA). Determination of whether HCs affect HIV-1 acquisition has been hampered by behavioral differences potentially confounding clinical observational data. Meta-analysis of these studies shows a significant association between DMPA use and increased risk of HIV-1 acquisition, raising important concerns. No association was found for combined oral contraceptives (COCs) containing levonorgestrel, nor for the two-monthly injectable contraceptive norethisterone enanthate (NET-EN), although data for NET-EN are limited. Susceptibility to HIV-1 and other sexually transmitted infections (STIs) may, however, be dependent on the type of progestin present in the formulation. Several underlying biological mechanisms that may mediate the effect of HCs on HIV-1 and other STI acquisition have been identified in clinical, animal, and ex vivo studies. A significant gap exists in the translation of basic research into clinical practice and public health policy. To bridge this gap, we review the current knowledge of underlying mechanisms and biological effects of commonly used progestins. The review sheds light on issues critical for an informed choice of progestins for the identification of safe, effective, acceptable and affordable contraceptive methods.

Janet P Hapgood, Charu Kaushic, Zdenek Hel

Healio report
Endocrine Reviews abstract

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