Association between use of the progestin Depot Medroxyprogesterone Acetate and Female Cervicovaginal Lavage Proinflammatory Cytokines among HIV-1 and HSV-2 co-infected African women: a case control study

Abstract

BackgroundUse of the progestin contraceptive Depot Medroxyprogesterone Acetate (DMPA) by HIV 1 infected women is associated with increased female to male transmission of HIV. Mucosal innate immune activation has been proposed as a likely mechanism. To establish the effect of DMPA upon mucosal immune activation, this study sought to evaluate the concentrations of 5 proinflammatory and the regulatory cytokine IL 10 in cervicovaginal lavage fluid.\n\nMethodsThis was a case control study, 70 participants were recruited, comprising of 35 asymptomatic ART naive HIV positive women on DMPA recruited as cases and 35 age matched asymptomatic ART naive HIV positive women not on contraceptives recruited as controls. Peripheral blood CD4 and total lymphocyte counts, High vaginal swab microscopy, endocervical smears and cervical cytology were performed for each participant. Concentrations of six proinflammatory cytokines were measured on cervicovaginal lavage by multiplex cytometric bead array.\n\nResultsThe mean age of cases was 26.8 years and 30 years for controls. Total lymphocyte counts and CD4 cell counts were significantly higher among cases (p=0.02 and 0.004 respectively). HSV 2 prevalence as determined by ELISA was higher (p=0.034 among cases. The concentrations of the cytokines IL 1{beta}, IL 6, IL 8, IL 12p70 and TNF were lower among cases, with IL 1{beta} being statistically significant (p=0.046). Concentrations of IL 10 was higher among cases (p=0.022). On multivariate analysis, reduction in IL 1{beta} and IL 8 were associated with the duration of DMPA use (p=0.015 and 0.041 respectively). Inclusion of HSV 2 into the multivariate models showed elevation of all cytokines measured (p=<0.001).\n\nConclusionDMPA use is associated with reduction of proinflammatory cytokines and elevation of the regulatory cytokine IL 10. This may explain increased female to male transmission of HIV infection by modulation of male genital tract mucosa in the absence of increased HIV 1 genital shedding.