HIV-NAT, TRCARC, Bangkok, Thailand.
Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil.
AIDS. 2021 Jul 15;35(9):1439-1449. doi: 10.1097/QAD.0000000000002901.
To evaluate associations between hair antiretroviral hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes.
Analysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line protease inhibitor-based antiretroviral therapy (ART) but were susceptible to at least one nucleoside reverse transcriptase inhibitor (NRTI) and their protease inhibitor, and continued taking their protease inhibitor-based regimen.
Antiretroviral hair concentrations in participants taking two NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography--tandem-mass-spectrometry assays. Participants' self-reported percentage of doses taken in the previous month; virologic failure was confirmed HIV-1 RNA at least 1000 copies/ml at week 24 or 48.
From 181 participants with hair samples (61% women, median age: 39 years; CD4+ cell count: 167 cells/μl; HIV-1 RNA: 18 648 copies/ml), 91 (50%) experienced virologic failure at either visit. At 24 weeks, median hair concentrations were 2.95 [interquartile range (IQR) 0.49-4.60] ng/mg for atazanavir, 2.64 (IQR 0.73--7.16) for lopinavir, and 0.44 (IQR 0.11--0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with virologic failure, the hazard ratio (95% CI) for ATV, LPV, and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27), respectively.
Protease inhibitor hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of second-line treatment failure in need of interventions.
评估头发中抗逆转录病毒浓度（作为累积药物依从性的客观指标）与自我报告的依从性和病毒学结果之间的关联。
对 ACTG-A5288 研究队列 A 的分析。这些在资源有限环境中接受二线基于蛋白酶抑制剂的抗逆转录病毒治疗（ART）失败的患者，但对至少一种核苷逆转录酶抑制剂（NRTI）及其蛋白酶抑制剂敏感，且继续服用其基于蛋白酶抑制剂的方案。
使用液相色谱-串联质谱法分析 181 名参与者（服用两种 NRTI 加增效后的阿扎那韦[n=69]或洛匹那韦[n=112]）在第 12、24、36 和 48 周时的头发中的抗逆转录病毒浓度。参与者在过去一个月内服用的剂量比例通过自我报告；病毒学失败是指在第 24 或 48 周时 HIV-1 RNA 至少为 1000 拷贝/ml。
在 181 名有头发样本的参与者（61%为女性，中位年龄：39 岁；CD4+细胞计数：167 个/μl；HIV-1 RNA：18648 拷贝/ml）中，91 名（50%）在任何一次就诊时都出现病毒学失败。在 24 周时，阿扎那韦的中位头发浓度为 2.95 [四分位距（IQR）0.49-4.60] ng/mg，洛匹那韦为 2.64（IQR 0.73-7.16），利托那韦为 0.44（IQR 0.11-0.76）。在第 24 和 48 周时，血浆 HIV-1 RNA 与头发水平呈负相关（rs-0.46 至-0.74）。与自我报告的依从性（rs-0.03 至-0.24）相比，关联较弱。头发浓度下降与病毒学失败显著相关，ATV、LPV 和 RTV 的风险比（95%CI）分别为 0.69（0.56-0.86）、0.77（0.68-0.87）和 0.12（0.06-0.27）。
在该队列中，与自我报告的依从性相比，蛋白酶抑制剂头发浓度与随后的病毒学结果具有更强的关联。头发依从性指标可识别需要干预措施的二线治疗失败风险患者。
