Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women

Abstract

Objective: The effects of sex hormones on the immune defenses of the female genital mucosa and its susceptibility to infections are poorly understood. The injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may increase the risk for HIV-1 acquisition. We assessed the local concentration in the female genital mucosa of cationic polypeptides with reported antiviral activity in relation to DMPA use.

Methods: HIV-1-uninfected women were recruited from among couples testing for HIV in Nairobi, Kenya. Cervicovaginal secretion samples were collected, and the concentrations of HNP1-3, LL-37, lactoferrin, HBD-2, and SLPI were measured by enzyme-linked immunosorbent assays. Levels of cationic polypeptides in cervicovaginal secretions were compared between women who were not using hormonal contraception and those using DMPA, oral, or implantable contraception.

Results: Among 228 women, 165 (72%) reported not using hormonal contraception at enrollment, 41 (18%) used DMPA, 16 (7%) used an oral contraceptive, and 6 (3%) used a contraceptive implant. Compared with nonusers of hormonal contraception, DMPA users had significantly higher mean levels of HNP1-3 (2.38 vs. 2.04 log₁₀ ng/mL; P = 0.024), LL-37 (0.81 vs. 0.40 log10 ng/mL; P = 0.027), and lactoferrin (3.03 vs. 2.60 log₁₀ ng/mL; P = 0.002), whereas SLPI and HBD-2 were similar.

Conclusions: Although all analyzed cationic polypeptides have intrinsic antiviral capacity, their interaction and cumulative effect on female genital mucosa susceptibility to infections in vivo has yet to be unraveled. This study suggests a potential mechanism underlying the effect of DMPA on the innate immune defenses, providing a rationale to investigate its effect on HIV-1 acquisition risk.

Figure 1

Mean concentrations of cationic peptides in cervicovaginal sections (CVS) of HIV-1-uninfected women, stratified by hormonal contraceptive use. Concentrations are expressed as ng/ml. Error bars indicate the 95% confidence interval for the mean estimate. Thin horizontal lines indicate the mean concentration in women using no hormonal contraception. Bold horizontal lines indicate statistical significance at p < 0.05 (*) and p < 0.01 (**). Individuals with peptide levels below the lower limit of detection are indicated at the bottom of each plot. The lower limit of detection for HNP1–3 was 0.156 ng/ml, for LL-37 was 0.100 ng/ml, for SLPI was 0.0625 ng/ml, for lactoferrin was 0.400 ng/ml, and for HBD-2 was 0.0156 ng/ml.