Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens. This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI. Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54–1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30–1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31–1·68) or without (1·25, 1·13–1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10–1·40) and tenofovir alafenamide alone (1·22, 1·03–1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07–1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96–1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (p=0·46 for hypertension; p=0·31 for dyslipidaemia). Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV. The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.

中文翻译：

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与其他当代抗逆转录病毒治疗方案相比，接受整合酶链转移抑制剂、替诺福韦艾拉酚胺或两者治疗的患者的 BMI 变化与高血压和血脂异常风险之间的关联：一项来自 RESPOND 联盟队列的多中心、前瞻性观察研究


在多项临床试验和观察队列中，整合酶链转移抑制剂 (INSTI) 和替诺福韦艾拉酚胺与体重增加有关。然而，与 INSTI 和替诺福韦艾拉酚胺相关的体重增加是否会增加体重相关临床事件的风险尚不清楚。我们的目的是评估与其他当代治疗方案相比，接受 INSTI、替诺福韦艾拉酚胺或两者同时治疗的 HIV 感染者中，BMI 的变化是否会差异性增加高血压或血脂异常的风险。这项多中心、前瞻性观察性研究分析了 RESPOND 的前瞻性数据，RESPOND 是一个国际 HIV 队列联盟，该联盟于 2017 年开始招募，目前仍在 37 个欧洲国家和澳大利亚的 HIV 诊所和医院进行招募。如果参与者年满 18 岁或以上，接受包含 INSTI 的抗逆转录病毒治疗 (ART) 方案或当代非 INSTI，基线时没有高血压或血脂异常，并且有基线和至少两次随访的 BMI，血脂和血压测量。我们排除了没有基线 CD4 或 HIV RNA 结果的参与者以及接受与体重变化相关的非 ART 药物的参与者，包括抗精神病药和情绪稳定剂、皮质类固醇、胰岛素和胰岛素促分泌剂。他们从基线开始进行随访，直到最早的高血压或血脂异常事件、最后一次就诊或 2021 年 12 月 31 日（以较早者为准）。 主要结局是高血压和血脂异常的发生率，为此，我们使用根据时间更新的 BMI 进行调整的多变量泊松回归来确定接受 INSTI、替诺福韦艾拉酚胺或两者治疗的人群中未调整和调整后的高血压和血脂异常的发生率比 (IRR)，以及测试了随时间更新的 ART 方案和 BMI 之间的相互作用。在 35 941 RESPOND 参与者中，高血压分析包括 9704 名（7327 [75·5 %] 男性和 2377 [24·5%] 女性），5231 名（3796 [72·6%] 男性和 1435 [27·4] %] 女性）被纳入血脂异常分析中。在单变量模型中，高血压在接受替诺福韦艾拉酚胺 INSTI 治疗（IRR 1·70，95% CI 1·54–1·88）或不接受替诺福韦艾拉酚胺 INSTI 治疗（1·41、1·30–1）的个体中更为常见。 ·53) 与既不接受 INSTI 也不接受替诺福韦艾拉酚胺的患者进行比较。根据时间更新的 BMI 和混杂因素进行调整，降低了接受 INSTI 治疗（IRR 1·48、1·31–1·68）或不使用替诺福韦艾拉酚胺（1·25、1·13–1·39）的参与者的风险。同样，使用替诺福韦艾拉酚胺联合 INSTI (IRR 1·24、1·10–1·40) 和单独使用替诺福韦艾拉酚胺 (1·22、1·03–1·44) 的参与者比不使用两者的参与者更常见INSTI 也不是替诺福韦艾拉酚胺。对 BMI 和混杂因素的调整降低了接受替诺福韦艾拉酚胺联合 INSTI 治疗的参与者的风险（调整后的 IRR 1·21、1·07–1·37），而单独接受替诺福韦艾拉酚胺的参与者的风险变得不显着（1·15、 0·96–1·38）。接受不同 ART 方案的参与者之间，BMI 增加与高血压和血脂异常风险之间的关联没有差异（高血压 p=0·46；血脂异常 p=0·31）。 尽管不能完全排除残余混杂因素，但 INSTI 的使用与高血压发生有关，而替诺福韦艾拉酚胺的使用与血脂异常有关，后者的关联部分是由体重增加介导的。这些结果重申了对艾滋病毒感染者进行高血压和血脂异常筛查的必要性。 CHU St Pierre 布鲁塞尔 HIV 队列、奥地利 HIV 队列研究、澳大利亚 HIV 观察数据库、荷兰国家观察性 HIV 队列的艾滋病治疗评估、布莱顿 HIV 队列、克罗地亚国家 HIV 队列、EuroSIDA 队列、法兰克福 HIV 队列队列研究、格鲁吉亚国家艾滋病健康信息系统、尼斯 HIV 队列、ICONA 基金会、摩德纳 HIV 队列、PISCIS 队列研究、瑞士 HIV 队列研究、瑞典 InfCare HIV 队列、皇家免费 HIV 队列研究、圣拉斐尔科学研究所、波恩大学医院 HIV 队列、科隆大学 HIV 队列、默克生命科学公司、ViiV Healthcare 和吉利德科学公司。