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

TitleEffect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women.
Publication TypeJournal Article
Year of Publication2016
AuthorsWeinberg A, Park J-G, Bosch R, Cho A, Livingston E, Aweeka F, Cramer Y, D Watts H, Luque AE, Cohn SE
JournalJ Acquir Immune Defic Syndr
Volume71
Issue2
Pagination137-45
Date Published2016 Feb 1
ISSN1944-7884
KeywordsAdolescent, Adult, Biomarkers, Contraceptive Agents, Female, Delayed-Action Preparations, Female, HIV Infections, Humans, Immunity, Cellular, Inflammation, Injections, Intramuscular, Lymphocyte Activation, Medroxyprogesterone Acetate, Middle Aged, T-Lymphocytes, Regulatory, Young Adult
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.

DOI10.1097/QAI.0000000000000850
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID26413850
PubMed Central IDPMC4712075
Grant List1U01AI068636 / AI / NIAID NIH HHS / United States
1U01AI069471 / AI / NIAID NIH HHS / United States
1U01AI069481 / AI / NIAID NIH HHS / United States
1U01AI069511 / AI / NIAID NIH HHS / United States
1U01AI069513 / AI / NIAID NIH HHS / United States
1UL-1TR001111 / TR / NCATS NIH HHS / United States
N01HD33162 / HD / NICHD NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
P30 AI50410 / AI / NIAID NIH HHS / United States
U01 AI068632 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
UL-1RR02460 / RR / NCRR NIH HHS / United States
UL-1TR000150 / TR / NCATS NIH HHS / United States
UL1 TR000430 / TR / NCATS NIH HHS / United States
UM1 AI068616 / AI / NIAID NIH HHS / United States
UM1 AI068632 / AI / NIAID NIH HHS / United States
UM1 AI068632 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069423-08 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1 AI106716 / AI / NIAID NIH HHS / United States