Centre for Experimental Pathogen Host Research, School of Medicine, University College Dublin, Dublin, Ireland.
St Vincent's University Hospital, Dublin, Ireland.
J Int AIDS Soc. 2021 Apr;24(4):e25702. doi: 10.1002/jia2.25702.
Although weight gain has been reported with the use of integrase strand transfer inhibitors (InSTI), concurrent use of tenofovir alafenamide (TAF) has been implicated in recent studies. This study examined weight changes in people living with HIV (PLWH) who switched from tenofovir disoproxil fumarate (TDF) to TAF, to clarify the relative contribution to weight gain of core agents versus TDF to TAF switch.
Antiretroviral-experienced, virologically suppressed PLWH in the U.S. OPERA cohort were included if they switched from TDF to TAF (5NOV2015-28FEB2019) and either maintained all other antiretrovirals or switched from a non-InSTI to an InSTI. Linear mixed models were used to assess weight changes before/after the switch to TAF (restricted cubic splines on time) and rates of change over time (linear splines on time, based on the shape of the weight change curves). Changes in weight on TDF or TAF were assessed among those who maintained other antiretrovirals (overall, by core class), and those who maintained an InSTI or switched to an InSTI (by core agent). All models were adjusted for age, sex, race, (age-sex, race-sex interactions), BMI, CD4 cell count, endocrine disorders and concurrent medications that could affect weight.
A total of 6908 PLWH were included, with 5479 maintaining all other antiretrovirals (boosted protease inhibitor: 746, non-nucleoside reverse transcriptase inhibitor: 1452, InSTI: 3281) and 1429 switching from a non-InSTI to an InSTI (elvitegravir/cobicistat: 1120, dolutegravir: 174, bictegravir: 129). In adjusted models, modest weight gain was observed over time on TDF for most (0.24 to 0.71 kg/year); raltegravir was the exception with weight loss. Switching to TAF was associated with early, pronounced weight gain for all (1.80 to 4.47 kg/year). This effect with TAF switch was observed both in PLWH maintaining other antiretrovirals and those switching to an InSTI, regardless of which InSTI agent was used. Weight gain tended to slow down or plateau approximately nine months after switch to TAF.
In this large, diverse U.S. cohort of PLWH, switching from TDF to TAF was associated with pronounced weight gain immediately after switch, regardless of the core class or core agent, suggesting an independent effect of TAF on weight gain.
尽管有报道称使用整合酶链转移抑制剂（INSTI）会导致体重增加，但最近的研究表明，同时使用替诺福韦艾拉酚胺（TAF）也与体重增加有关。本研究旨在检查从替诺福韦二吡呋酯（TDF）转换为 TAF 的 HIV 感染者（PLWH）的体重变化，以阐明核心药物与 TDF 转换为 TAF 对体重增加的相对贡献。
在美国 OPERA 队列中，纳入了接受过抗逆转录病毒治疗、病毒学抑制的 PLWH，如果他们从 TDF 转换为 TAF（2015 年 11 月 5 日至 2019 年 2 月 28 日），并且维持其他所有抗逆转录病毒药物，或者从非 INSTI 转换为 INSTI。使用线性混合模型评估 TAF 转换前后的体重变化（时间受限立方样条）和随时间变化的体重变化率（基于体重变化曲线形状的线性样条）。在维持其他抗逆转录病毒药物的患者（总体上，按核心类别）和维持 INSTI 或转换为 INSTI 的患者（按核心药物）中评估 TDF 或 TAF 上的体重变化。所有模型均根据年龄、性别、种族（年龄性别、种族性别交互作用）、BMI、CD4 细胞计数、内分泌紊乱和可能影响体重的同时使用的药物进行调整。
共纳入 6908 名 PLWH，其中 5479 名患者维持其他所有抗逆转录病毒药物（增效蛋白酶抑制剂：746 名，非核苷类逆转录酶抑制剂：1452 名，INSTI：3281 名），1429 名患者从非 INSTI 转换为 INSTI（elvitegravir/cobicistat：1120 名，多替拉韦：174 名，比克替拉韦：129 名）。在调整后的模型中，TDF 治疗期间大多数患者的体重随时间呈适度增加（0.24 至 0.71kg/年）；raltegravir 是体重减轻的例外。转换为 TAF 后，所有患者的体重在早期均有明显增加（1.80 至 4.47kg/年）。在维持其他抗逆转录病毒药物的 PLWH 和转换为 INSTI 的患者中，均观察到 TAF 转换后的这种影响，无论使用哪种 INSTI 药物。大约在转换为 TAF 后九个月，体重增加的速度趋于放缓或达到平台期。
在这项来自美国的大型、多样化的 PLWH 队列中，从 TDF 转换为 TAF 后立即出现明显的体重增加，无论核心药物类别或核心药物如何，均提示 TAF 对体重增加有独立影响。
