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Initiation of antiretroviral therapy differentially influences genital and systemic immune activation in HIV-infected women.
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2020-10-05 , DOI: 10.1089/aid.2019.0268 Smritee Dabee 1 , Nonhlanhla N Mkhize 2 , Heather B Jaspan 1, 3 , David Lewis 4, 5 , Pamela P Gumbi 6 , Jo-Ann S Passmore 1, 7, 8
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2020-10-05 , DOI: 10.1089/aid.2019.0268 Smritee Dabee 1 , Nonhlanhla N Mkhize 2 , Heather B Jaspan 1, 3 , David Lewis 4, 5 , Pamela P Gumbi 6 , Jo-Ann S Passmore 1, 7, 8
Affiliation
Antiretroviral therapy (ART) has significantly improved the quality of life of HIV-infected individuals: reducing plasma viremia, restoring CD4+ T cell numbers, and correcting imbalances in blood memory T cell subsets. While ART improves immune correlates at mucosal sites, including the lower female genital tract (FGT), ART initiation has been associated with reactivation of common FGT infections. We investigated the effect of ART on immune activation and inflammation in the genital tract. We measured blood and genital T cell activation, proliferation, and immunosenescence (CD38, HLADR, Ki67, CD127, and CD57), and cytokine levels in women on ART for ∼7 years (cross-sectional analysis) or initiating ART (immediately before and 1 month after). Effector memory T cells predominated in blood and FGT during chronic infection, irrespective of ART status. In women initiating ART, 1 month was insufficient for T cell reconstitution, or alterations in T cell subset distribution, despite both plasma and genital viral loads decreasing to undetectable levels in most participants. Initiating ART was accompanied by a decline in plasma IP-10 that correlated with decreased blood CD38 expression in blood (p = .0204) but not in the FGT. The reduction in plasma (but not genital) cytokine levels due to ART initiation was dependent on their concentrations before treatment. While T cell activation decreased significantly in blood (CD4: p = .032; CD8: p = .0137), activation levels remained similar in the genital tract despite 1 month of treatment. Overall, the decrease in cellular activation and inflammation seen in blood with ART initiation was not evident in the FGT.
中文翻译:
抗逆转录病毒治疗的启动对 HIV 感染妇女的生殖器和全身免疫激活有不同的影响。
抗逆转录病毒疗法 (ART) 显着改善了 HIV 感染者的生活质量:减少血浆病毒血症,恢复 CD4 +T 细胞数量,以及纠正血液记忆 T 细胞亚群的不平衡。虽然 ART 可改善粘膜部位的免疫相关性,包括女性下生殖道 (FGT),但 ART 的启动与常见 FGT 感染的再激活有关。我们研究了 ART 对生殖道免疫激活和炎症的影响。我们测量了接受 ART 约 7 年(横断面分析)或开始 ART(紧接在和1 个月后)。无论 ART 状态如何,慢性感染期间效应记忆 T 细胞在血液和 FGT 中占主导地位。在开始 ART 的女性中,1 个月不足以进行 T 细胞重建或 T 细胞亚群分布的改变,尽管血浆和生殖器病毒载量在大多数参与者中都降至检测不到的水平。启动 ART 伴随着血浆 IP-10 的下降,这与血液中 CD38 的表达下降有关。p = .0204)但不在 FGT 中。由于 ART 启动而导致血浆(但不是生殖器)细胞因子水平的降低取决于它们在治疗前的浓度。虽然血液中的 T 细胞活化显着降低(CD4:p = .032 ;CD8:p = .0137),但尽管治疗 1 个月,生殖道中的活化水平仍然相似。总体而言,在 FGT 中,ART 启动后血液中细胞活化和炎症的减少并不明显。
更新日期:2020-10-07
中文翻译:
抗逆转录病毒治疗的启动对 HIV 感染妇女的生殖器和全身免疫激活有不同的影响。
抗逆转录病毒疗法 (ART) 显着改善了 HIV 感染者的生活质量:减少血浆病毒血症,恢复 CD4 +T 细胞数量,以及纠正血液记忆 T 细胞亚群的不平衡。虽然 ART 可改善粘膜部位的免疫相关性,包括女性下生殖道 (FGT),但 ART 的启动与常见 FGT 感染的再激活有关。我们研究了 ART 对生殖道免疫激活和炎症的影响。我们测量了接受 ART 约 7 年(横断面分析)或开始 ART(紧接在和1 个月后)。无论 ART 状态如何,慢性感染期间效应记忆 T 细胞在血液和 FGT 中占主导地位。在开始 ART 的女性中,1 个月不足以进行 T 细胞重建或 T 细胞亚群分布的改变,尽管血浆和生殖器病毒载量在大多数参与者中都降至检测不到的水平。启动 ART 伴随着血浆 IP-10 的下降,这与血液中 CD38 的表达下降有关。p = .0204)但不在 FGT 中。由于 ART 启动而导致血浆(但不是生殖器)细胞因子水平的降低取决于它们在治疗前的浓度。虽然血液中的 T 细胞活化显着降低(CD4:p = .032 ;CD8:p = .0137),但尽管治疗 1 个月,生殖道中的活化水平仍然相似。总体而言,在 FGT 中,ART 启动后血液中细胞活化和炎症的减少并不明显。