title: Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women.
abstract: OBJECTIVE
  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.
authors.affiliation: *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.
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
authors.forename: Jeong-Gun
authors.initials: JG
authors.lastname: Park
authors.forename: Ronald
authors.initials: R
authors.lastname: Bosch
authors.forename: Alice
authors.initials: A
authors.lastname: Cho
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Livingston
authors.forename: Fran
authors.initials: F
authors.lastname: Aweeka
authors.forename: Yoninah
authors.initials: Y
authors.lastname: Cramer
authors.forename: D Heather
authors.initials: DH
authors.lastname: Watts
authors.forename: Amneris E
authors.initials: AE
authors.lastname: Luque
authors.forename: Susan E
authors.initials: SE
authors.lastname: Cohn
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects*; D003692:Delayed-Action Preparations; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007249:Inflammation; D007273:Injections, Intramuscular; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D017258:Medroxyprogesterone Acetate