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

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

Author information

1
*Department of Pediatrics, University of Colorado Denver Anschutz Medical Center, Aurora, CO; †Department of Biostatistics, Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA; ‡Department of Obstetrics/Gynecology/Maternal-Fetal Medicine, Duke University Medical Center, Durham, NC; §Department of Clinical Pharmacology, University of California, San Francisco, CA; ‖Office of the Global AIDS Coordinator and Health Diplomacy, U.S. Department of State, Washington, DC; ¶Department of Infectious Diseases, University of Rochester School of Medicine and Dentistry, Rochester, NY; and #Department of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL.

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.

PMID:
26413850
PMCID:
PMC4712075
DOI:
10.1097/QAI.0000000000000850
[Indexed for MEDLINE]
Free PMC Article

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