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

Adriana Weinberg, Jeong Gun Park, Ronald Bosch, Alice Cho, Elizabeth Livingston, Fran Aweeka, Yoninah Cramer, D. Heather Watts, Amneris E. Luque, Susan E. Cohn

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 (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 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 C max 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.

Original languageEnglish (US)
Pages (from-to)137-145
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume71
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Medroxyprogesterone Acetate
Acetates
HIV
T-Lymphocytes
Cellular Immunity
Human Herpesvirus 3
Area Under Curve
Interleukin-2
Phytohemagglutinins
Interleukin-10
Disease Progression
Color
Biomarkers
Lymphocytes
RNA
Inflammation

Keywords

  • cell-mediated immunity
  • depot medroxyprogesterone acetate
  • HIV infection
  • hormonal contraception

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women. / Weinberg, Adriana; Park, Jeong Gun; Bosch, Ronald; Cho, Alice; Livingston, Elizabeth; Aweeka, Fran; Cramer, Yoninah; Watts, D. Heather; Luque, Amneris E.; Cohn, Susan E.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 71, No. 2, 01.02.2016, p. 137-145.

Research output: Contribution to journalArticle

Weinberg, Adriana ; Park, Jeong Gun ; Bosch, Ronald ; Cho, Alice ; Livingston, Elizabeth ; Aweeka, Fran ; Cramer, Yoninah ; Watts, D. Heather ; Luque, Amneris E. ; Cohn, Susan E. / Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women. In: Journal of Acquired Immune Deficiency Syndromes. 2016 ; Vol. 71, No. 2. pp. 137-145.
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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 (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 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 C max 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.",
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AU - Cho, Alice

AU - Livingston, Elizabeth

AU - Aweeka, Fran

AU - Cramer, Yoninah

AU - Watts, D. Heather

AU - Luque, Amneris E.

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