Abstract

Depot medroxyprogesterone acetate (DMPA) is the most common hormonal contraceptive used by women in sub-Saharan Africa, however, it has been epidemiologically associated with HIV infections. To assess whether DMPA has an effect on the number and activation of HIV target cells, this study assessed the levels and phenotype of blood- and mucosal-derived HIV target cells among women using DMPA. Thirty-five HIV uninfected women from the Pumwani Sex Worker cohort from Nairobi, Kenya were enrolled in the study (15 using DMPA and 20 not using hormonal contraception). Blood (plasma and peripheral blood mononuclear cells) and cervicovaginal (lavage, cervical cells, and ectocervical biopsies) samples were collected. Cellular phenotype and activation status were determined by flow cytometry, cytokine levels were assessed by bead array and image analysis assessed cell number and phenotype in situ. In blood, the proportion of HIV target cells and activated T cells was lower in DMPA users versus those not using hormonal contraceptives. However, analysis of cervical mononuclear cells showed that DMPA users had elevated levels of activated T cells (CD4+CD69+) and expressed lower levels of the HIV co-receptor CCR5 on a per cell basis, while tissue samples showed that in the ectocervix, DMPA users had a higher proportion of CD4+CCR5+ T cells. This study demonstrates that DMPA users had higher levels of activated T cells and HIV target cells in the genital tract. The increased pool of mucosal HIV target cells provides new biological information about the potential impact of DMPA on HIV susceptibility.

Highlights

  • Access to hormonal contraception (HC) enables women to make choices about their reproductive health

  • A significant difference was observed for the duration of self-reported sex work (DMPA users median of 21 vs. 30 months in the not taking hormonal contraception (no HC) group, p = .01) and the practice of vaginal douching (DMPA 47% vs. no HC 10%, p = .02)

  • Women using Depot medroxyprogesterone acetate (DMPA) had a lower portion of activated CD4+ cells in their blood compartment when compared with the no HC users

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Summary

Introduction

Access to hormonal contraception (HC) enables women to make choices about their reproductive health. Long-term hormonal contraceptives such as injectable contraceptives are common, in younger women, mostly due to their ease of use. Depot medroxyprogesterone acetate (DMPA) is an intramuscular injectable progestin that is administrated once every 3 months. DMPA is the most common HC used in subSaharan Africa in women between the ages of 18–49 years.[1] Simultaneously, this group is significantly overrepresented in the number of new HIV infections.[2] Recently, metaanalyses have reported that DMPA use was associated with about 1.4-fold increase in risk of HIV infection.[3,4,5] Understanding how DMPA might affect the susceptibility to HIV infection at the cellular and molecular level is essential for the development of new policies on its use

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