Weinberg Adriana, Park Jeong-Gun, Bosch Ronald, Cho Alice, Livingston Elizabeth, Aweeka Fran, Cramer Yoninah, Watts D Heather, Luque Amneris E, Cohn Susan E
*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.
J Acquir Immune Defic Syndr. 2016 Feb 1;71(2):137-45. doi: 10.1097/QAI.0000000000000850.
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).
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].
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.
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.
在未接受治疗的女性中，醋酸甲羟孕酮长效注射剂（DMPA）与HIV传播增加及疾病进展加速有关。潜在的潜在机制包括免疫调节。我们评估了单次注射DMPA对接受联合抗逆转录病毒治疗（cART）的HIV感染女性的细胞介导免疫（CMI）、T细胞活化、T细胞调节（Treg）和炎症的影响。
血浆HIV RNA≤400拷贝/毫升且cART治疗稳定的女性接受DMPA治疗，并在基线、4周[甲羟孕酮（MPA）浓度峰值（Cmax）]和12周[浓度曲线下MPA最高面积]时进行免疫学和MPA测量。
基线时，24名中位年龄为32岁、每微升有622个CD4(+)细胞的女性中，≥68%的人通过淋巴细胞增殖和/或IFNγ/IL2双色荧光斑点法检测了HIV、水痘带状疱疹病毒、植物血凝素A和CD3/CD28 CMI。DMPA给药后CMI无显著变化，但在第12周时，水痘带状疱疹病毒IL2/IFNγ荧光斑点增加了1.4倍。DMPA给药后T细胞活化降低，在第12周时CD4(+)CD25+%达到统计学显著性。Treg表现各异，第4周时CD8+FOXP3+%增加，第12周时CD4+IL35+%减少。第12周时TGFβ降低，血浆生物标志物无其他变化。相关性分析表明，高MPA Cmax和/或浓度曲线下面积与从基线到第4周和/或第12周时IFNγ HIV酶联免疫斑点、CD4+IL35+%和CD4+TGFβ+% Treg增加以及血浆IL10降低显著相关。
单剂量DMPA对接受cART的HIV感染女性没有免疫抑制或促炎作用。需要进一步研究评估多剂量的影响。
