Systemic immune activation (IA) is a proven key factor in human immunodeficiency virus type 1 (HIV) infection pathogenesis and progression to acquired immunodeficiency syndrome. The reproductive hormone progesterone plays a role in regulating the immune system, and most cells contain progesterone receptors. Previous studies have linked high-progestogen states in women, such as pregnancy and progestin-based contraception use, to increased infectivity in HIV-seropositive women and increased HIV acquisition in seronegative women. Progestin-based contraceptives such as depot-medroxyprogesterone acetate (DMPA) can create high plasma levels of progesterone analogs. Therefore, studying DMPA use by HIV-seropositive and seronegative women may clarify DMPA’s role in HIV-related IA and genital shedding, and immune changes related to HIV acquisition. We hypothesize that DMPA increases systemic IA. Increased IA could be clinically significant by contributing to increased HIV acquisition in high-risk HIV-seronegative women, and by increasing genital shedding and infectivity among HIV-seropositive women. To answer this question, peripheral blood mononuclear cells (PBMC) were collected at three postpartum time points over six months from 120 Kenyan women with both HIV-seropositive and seronegative status, including a sub-population in each category that elected to receive DMPA for contraception. Two immunophenotyping panels were developed to measure T-cell IA and cellular subsets of interest using flow cytometry (CD38, HLA-DR, Ki-67, Bcl-2 for T-cell activation; FOXP3, CD25, CD127 for regulatory T-cells; CCR7, CD45RA, CD27, CD28, CD57 for memory subsets; CCR5 for the HIV co-receptor). With preliminary analysis completed for most samples, specific antibody populations have been gated with FlowJo software. After completion, we will compare different population percentages in the four arms of the study, observing how these change with DMPA administration. These calculations will help elucidate expected differences in inflammatory and regulatory changes in both HIV-seropositive and seronegative women with respect to the relationships between DMPA, immune activation, and HIV susceptibility and infectivity.