Women using the injectable progestin contraceptive depot medroxyprogesterone acetate, or DMPA, may face a substantially elevated risk for HIV infection compared with other forms of hormonal birth control, 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, 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 3-monthly injectable contraceptive, Depo-Provera, acts differently to other progestins widely used in contraceptives,” Janet P. Hapgood, PhD, 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, told Infectious Disease News. “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 estrogen may exert a protective, antiviral effect. In a review of animal, cell and biochemical research on MPA, 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 that 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, nonhormonal 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 nonhormonal contraceptives on HIV-1 acquisition. Combined evidence supports a focus on methods that avoid progestins with relatively potent glucocorticoid receptor activity, such as MPA.” – by Regina Schaffer
- Hapgood JP, et al. Endocr Rev. 2018;doi:10.1210/er.2017-00103.
Disclosures: The NIH and the Canadian Institutes of Health Research supported the study.