Rugemalila Joan, Ndege Robert, Kunambi Peter, Shabani Siraji, Sambu Veryeh, Rwebemberwa Anath, Kalluvya Samuel, Sunguya Bruno, Nagu Tumaini, Aboud Said
Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Department of Internal Medicine, Muhimbili National Hospital, Dar es Salaam, Tanzania.
J Antimicrob Chemother. 2025 Jun 3;80(6):1694-1701. doi: 10.1093/jac/dkaf125.
People living with HIV (PLHIV) who fail first-line ART have a higher risk of failing subsequent ART. We examined viral suppression (VS) among adolescents and youths (AY) failing PI ART in Tanzania.
We conducted a retrospective study nested within a national third-line cohort of PLHIV. We analysed data of 147 AY (aged 10-24 years) with failure of PI-based ART between 2020 and 2022 who were followed for 12 months to assess for VS. Descriptive statistics were summarized by demographics and clinical characteristics, and we used logistic regression to assess factors associated with virological failure (VF) and drug resistance mutations (DRMs).
More than 40% of 147 participants had HIV subtype A, 52% (76/147) harboured major PI DRMs and 35% had NRTI mutations. A PI regimen at ART initiation was associated with a major PI DRM adjusted relative risk (aRR) of 1.66 (95% CI: 1.13-2.44; P = 0.010). Among participants with major PI DRMs, 12.2% had intermediate to high levels of resistance to lopinavir and atazanavir, and 2.1% to darunavir, respectively. V82A was the most frequent PI DRM; NRTI mutations included thymidine analogue mutations and absent K65R. VS occurred in 65% of AY who had PI DRMs compared with 45% of those without DRMs; this difference was not statistically significant.
More than half of AY who had PI DRMs had a higher proportion of early VS (65%) compared with those without DRMs (45%). Optimal viral load monitoring, adherence intensification and routine drug resistance testing are key strategies to improve VS.
一线抗逆转录病毒治疗（ART）失败的艾滋病毒感染者（PLHIV）后续ART失败风险更高。我们在坦桑尼亚对接受蛋白酶抑制剂（PI）ART治疗失败的青少年和青年（AY）中的病毒抑制（VS）情况进行了研究。
我们在一个全国性的PLHIV三线队列中进行了一项回顾性研究。我们分析了2020年至2022年间147名年龄在10至24岁、基于PI的ART治疗失败且随访12个月以评估VS情况的AY的数据。描述性统计按人口统计学和临床特征进行总结，我们使用逻辑回归评估与病毒学失败（VF）和耐药突变（DRM）相关的因素。
147名参与者中超过40%感染HIV A亚型，52%（76/147）携带主要PI DRM，35%有核苷类逆转录酶抑制剂（NRTI）突变。ART起始时使用PI方案与主要PI DRM调整相对风险（aRR）为1.66相关（95%置信区间：1.13 - 2.44；P = 0.010）。在有主要PI DRM的参与者中，分别有12.2%对洛匹那韦和阿扎那韦有中度至高度耐药，2.1%对达芦那韦有耐药。V82A是最常见的PI DRM；NRTI突变包括胸苷类似物突变且无K65R。有PI DRM的AY中65%实现了VS，无DRM的AY中这一比例为45%；这一差异无统计学意义。
有PI DRM的AY中超过一半（65%）的早期VS比例高于无DRM的AY（45%）。优化病毒载量监测、加强依从性和常规耐药检测是改善VS的关键策略。
