Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression.
Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression.
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DOI：
10.1097/qai.0000000000001629
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发表时间：
2018-04-15
期刊：
影响因子：
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通讯作者：
Siedner MJ
中科院分区：
文献类型：
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作者：
Castillo-Mancilla JR;Morrow M;Boum Y;Byakwaga H;Haberer JE;Martin JN;Bangsberg D;Mawhinney S;Musinguzi N;Huang Y;Tracy RP;Burdo TH;Williams K;Muzzora C;Hunt PW;Siedner MJ
尽管进行了抑制性抗逆转录病毒治疗（ART），残留的全身炎症仍然存在，并且与非艾滋病临床结果相关。我们的目的是评估乌干达 HIV 感染者的 ART 依从性与炎症之间的关系，这些人主要接受基于奈韦拉平的 ART（具有胸苷类似物骨架），并通过常规检测进行病毒学抑制。在基线时和开始 ART 后 6 个月，对血浆 HIV RNA 达到检测不到的未接受治疗的成年人测量白细胞介素 6 (IL-6)、D-二聚体、可溶性 (s)CD14、sCD163、犬尿氨酸/色氨酸 (K/T) 比率以及 CD8+ T 细胞激活的血浆浓度。 在他们为期 6 个月的访问中。依从性通过药物事件监测系统（MEMS）进行测量，并计算为每个参与者观察到/规定的设备开口的比率。我们拟合调整后的线性回归模型来估计 ART 依从性与炎症生物标志物的对数转换血浆浓度之间的关联。我们评估了 282 名参与者，中位年龄 35 岁，其中 70% 是女性。中位 (IQR) 依从率为 93 (84, 98) %。在调整后的分析中，平均ART依从性每增加10%，我们发现IL-6、D-二聚体和IL-6、D-二聚体和IL-6的水平分别减少15%（P<0.0001, 95% CI -21.0, -7.9）、11%（P=0.017, -18.3, -2.0）和3%（P=0.028, -5.0, -0.3）。分别为sCD14。乌干达 HIV 感染者在接受 ART 治疗后不久就实现了病毒抑制，较高的 ART 依从性与较低水平的炎症、免疫激活和凝血病生物标志物相关。这表明坚持抗逆转录病毒治疗可能会产生病毒抑制以外的生物学后果。病毒学抑制个体的 ART 依从性优化是否可以减少残留炎症仍不清楚。
Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, the kynurenine/tryptophan (K/T) ratio, in addition to CD8+ T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naïve adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit. Adherence was measured through medication event monitoring system (MEMS) and calculated as the ratio of observed/prescribed device openings per participant. We fit adjusted linear regression models to estimate the association between ART adherence and the log-transformed plasma concentrations of inflammatory biomarkers. We evaluated 282 participants, median age 35 years, 70% women. The median (IQR) adherence was 93 (84, 98) %. In the adjusted analyses, for every 10% increase in average ART adherence, we found a 15% (P<0.0001, 95% CI −21.0, −7.9), 11% (P=0.017, −18.3, −2.0) and 3% (P=0.028, −5.0, −0.3) decrease in IL-6, D-dimer and sCD14, respectively. Higher ART adherence was associated with lower levels of biomarkers of inflammation, immune activation and coagulopathy among Ugandans living with HIV who achieved viral suppression shortly after ART initiation. This suggests that ART adherence could have biological consequences beyond viral suppression. Whether ART adherence optimization in virologically-suppressed individuals could reduce residual inflammation remains unknown.