Effect Of Depot Medoxyprogesterone Acetate On Immune Functions And Inflammatory Markers Of Hiv-Infected Women

Objectives:Depot medroxyprogesterone acetate (DMPA) was associated with increased HIV transmission and accelerated disease progression in untreated women. The potential underlying mechanisms include immune modulation. We evaluated the effect of a single DMPA injection on cell-mediated immunity (CMI), T-cell activation, T-cell regulation (Treg), and inflammation in HIV-infected women on combination antiretroviral regimen (cART).Methods:Women with HIV plasma RNA 400 copies per milliliter on stable cART received DMPA and had immunologic and medroxyprogesterone acetate (MPA) measurements at baseline, 4 weeks [peak MPA concentration (C-max)], and 12 weeks [highest MPA area under the concentration curve].Results:At baseline, among 24 women with median age of 32 years and 622 CD4(+) cells per microliter, 68% had HIV, varicella-zoster virus, phytohemagglutinin A and CD3/CD28 CMI measured by lymphocyte proliferation, and/or IFN/IL2 dual-color fluorospot. CMI did not significantly change after DMPA administration except for a 1.4-fold increase in IL2/IFN varicella-zoster virus fluorospot at week 12. T-cell activation decreased after DMPA administration, reaching statistical significance at week 12 for CD4(+)CD25+%. Treg behaved heterogeneously with an increase in CD8+FOXP3+% at week 4 and a decrease in CD4+IL35+% at week 12. There was a decrease in TGF at week 12 and no other changes in plasma biomarkers. Correlation analyses showed that high MPA C-max and/or area under the concentration curve were significantly associated with increases of IFN HIV enzyme-linked ImmunoSpot, CD4+IL35+%, and CD4+TGF+% Treg and decreases of plasma IL10 from baseline to weeks 4 and/or 12.Conclusions:A single dose of DMPA did not have immune-suppressive or pro-inflammatory effects in HIV-infected women on cART. Additional studies need to assess the effect of multiple doses.