Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women

J Acquir Immune Defic Syndr. 2016 Feb 1;71(2):137-45. doi: 10.1097/QAI.0000000000000850.

Abstract

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 (Cmax)], 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 IFNγ/IL2 dual-color fluorospot. CMI did not significantly change after DMPA administration except for a 1.4-fold increase in IL2/IFNγ 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 TGFβ at week 12 and no other changes in plasma biomarkers. Correlation analyses showed that high MPA Cmax and/or area under the concentration curve were significantly associated with increases of IFNγ HIV enzyme-linked ImmunoSpot, CD4+IL35+%, and CD4+TGFβ+% 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / metabolism
  • Contraceptive Agents, Female / administration & dosage
  • Contraceptive Agents, Female / adverse effects*
  • Delayed-Action Preparations
  • Female
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • Humans
  • Immunity, Cellular / drug effects*
  • Inflammation
  • Injections, Intramuscular
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Medroxyprogesterone Acetate / administration & dosage
  • Medroxyprogesterone Acetate / adverse effects*
  • Middle Aged
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Young Adult

Substances

  • Biomarkers
  • Contraceptive Agents, Female
  • Delayed-Action Preparations
  • Medroxyprogesterone Acetate

Grant support