Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms

Abstract

Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition, concentration of the 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 depot medroxyprogesterone acetate. 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 depot medroxyprogesterone acetate use and increased risk of HIV-1 acquisition, raising important concerns. No association was found for combined oral contraceptives containing levonorgestrel, nor for the two-monthly injectable contraceptive norethisterone enanthate, although data for norethisterone enanthate are limited. Susceptibility to HIV-1 and other sexually transmitted infections 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 sexually transmitted infection acquisition have been identified in clinical, animal, and ex vivo studies. A substantial 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.

Medroxyprogesterone acetate mediated alteration in the vaginal microbiota and microenvironment in a Kenyan sex worker cohort

“…Circulating MPA, estradiol, and progesterone were quantified in study participants (Supplemental Figure 2A, B, C). As previously reported, use of DMPA was associated with hypo-estrogenism v(4, 24, 25); sex workers on DMPA had significantly lower levels of circulating estradiol compared to NH women (Supplemental Figure 2B). We also found DMPA was associated with significantly lower levels of circulating progesterone, as compared to NH sex workers and those on OCPs (Supplemental Figure 2C).…”

“…However, the VMB of sex workers on DMPA was significantly more diverse than NH (Figure 1C,1D), and OCP women (Figure 1C), as seen in Shannon Diversity rarefaction curves. To rule out that the bacterial diversity associated with DMPA might be due to a disproportionate number of women with intermediate (4-6) Nugent Scores, this group was removed from the analysis and Shannon Diversity was plotted in women with Nugent Scores 0-3 (Supplemental Figure 3; NH, N=18; OCP, N=13; DMPA, N=17). Even in this subset, the Shannon Diversity Index was significantly greater in sex workers on DMPA than NH, suggesting that DMPA is associated with enhanced bacterial diversity in the VMB of healthy, asymptomatic Kenyan sex workers.…”

“…These statistics are particularly troubling because DMPA is a popular contraceptive in Africa (3), where HIV-1 prevalence is greatest. Studies have suggested several biological mechanisms, including hypo-estrogenism, by which DMPA might enhance susceptibility to HIV-1 and other sexually transmitted infections (STIs) (4). However, few (5-10) examine the relationship between hormonal contraceptives and the vaginal microbiota (VMB), even though diverse VMB, low in Lactobacillus species, confers a 4-fold increased risk of HIV-1 (11).…”

Acquisition of Sexually Transmitted Infections among Women Using a Variety of Contraceptive Options: A prospective Study among High‐risk African Women

“…In these countries, STIs are the second leading cause of lost healthy life‐years in women of reproductive age because of their adverse effects on reproductive health . In addition, STIs increase the risk of HIV‐1 acquisition and transmission , providing further incentive to understand factors increasing STI susceptibility.…”

“…Hormonal contraceptives, including combined oral contraceptive pills, injectable depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET‐EN), and hormonal‐containing implants, are among the most widely used family planning methods in many countries where the burden of both HIV‐1 and other STIs is highest . Although the association between HIV‐1 acquisition and the use of hormonal contraception has been extensively studied , with the bulk of studies suggesting modestly elevated HIV‐1 risk for DMPA users, relatively fewer studies have examined STI acquisition among different groups of contraceptive users. Prior prospective studies examining the association between use of certain hormonal contraceptives and the risk of STIs have reported mixed findings , with some reporting a statistically significantly higher incidence of certain STIs among users of specific contraceptive methods while others found no association .…”