Weight gain among treatment-naive persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada
Weight gain among treatment-naive persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada
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DOI：
10.1002/jia2.25484
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发表时间：
2020-04-01
影响因子：
6
通讯作者：
Koethe, John R.
中科院分区：
文献类型：
--
作者：
Bourgi, Kassem;Jenkins, Cathy A.;Koethe, John R.
抗逆转录病毒治疗（ART）开始后体重增加是常见的，可能使一些HIV （PWH）患者易患心脏代谢疾病。我们在北美艾滋病研究与设计队列合作（NA-ACCORD）中评估了抗逆转录病毒药物类别与首次接受抗逆转录病毒治疗的PWH体重变化之间的关系。方法2007年1月1日至2016年12月31日期间，对NA-ACCORD启动整合酶链转移抑制剂（INSTI）、蛋白酶抑制剂（PI）或非核苷逆转录酶抑制剂（NNRTI）为基础的ART治疗的成人初始PWH进行随访。多变量线性混合效应模型估计了抗逆转录病毒治疗开始后5年的体重，调整了年龄、性别、种族、队列地点、HIV获取方式、治疗年份、基线体重、血浆HIV-1 RNA水平和CD4（+）细胞计数。由于接受较新INSTI药物的PWH随访时间较短，特定INSTI药物的权重估计为两年。二次分析使用逻辑回归和来自初次分析的所有协变量，评估了与2年和5年体重增加100 - 10%相关的因素。结果在22972名参与者中，87%为男性，41%为白人。49%的患者开始使用NNRTI， 31%的患者开始使用PI， 20%的患者开始使用基于isi的方案（raltegravir （RAL）为1624，elvitegravir （EVG）为2085，dolutegravir （DTG）为929）。PWH开始以isi为基础的治疗方案的5年平均体重变化估计为+5.9kg，而NNRTI组为+3.7kg， PI组为+5.5kg。在PWH起始INSTI药物中，平均估计两年体重变化为DTG +7.2kg, RAL +5.8kg和EVG +4.1kg。女性、基线CD4（+）细胞计数较低的人以及那些开始以胰岛素为基础的方案的人在两年内体重增加10%的几率更高（调整后的优势比= 1.37,95%置信区间：1.20至1.56 vs. NNRTI）。结论：与以nnrti为基础的方案相比，以PWH为基础的方案平均增加了更多的体重。这一现象可能反映了抗逆转录病毒药物对体重调节的异质性作用，有待进一步探讨。
Introduction Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naive PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).Methods Adult, treatment-naive PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4(+) cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.Results Among 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4(+) cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).Conclusions PWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.