抗逆转录病毒联合疗法F/TAF、E/C/F/TAF和R/F/TAF对健康志愿者胰岛素抵抗的影响：TAF-IR研究

Effects of antiretroviral combination therapies F/TAF, E/C/F/TAF and R/F/TAF on insulin resistance in healthy volunteers: the TAF-IR Study.

作者信息

Spinner Christoph D, Schulz Sebastian, Bauer Ulrike, Schneider Jochen, Bobardt Johanna, Von Werder Alexander, Schmid Roland M, Zink Alexander, Wolf Eva, Iakoubov Roman

机构信息

Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.

Department I of Dermatology and Allergology, University Hospital Klinikum rechts der Isar, Munich, Germany.

出版信息

Antivir Ther. 2018;23(7):629-632. doi: 10.3851/IMP3271. Epub 2018 Oct 3.

DOI:10.3851/IMP3271

PMID:30281025

Abstract

BACKGROUND

Increased insulin resistance (IR), associated with specific antiretroviral drugs or drug classes, is an established risk factor for type 2 diabetes in HIV patients, ultimately increasing morbidity and mortality. To date, data on the risk of IR in tenofovir alafenamide (TAF)-based protocols are unavailable.

METHODS

This prospective randomized, open-label study evaluated the effects of IR on 30 healthy volunteers receiving fixed-dose combinations (FDCs) of emtricitabine/tenofovir alafenamide (F/TAF), elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF). IR was measured before and after 14-day treatments using the hyperinsulinemic-euglycaemic clamp technique (HEGC). Changes in IR in each group were evaluated using the mean glucose disposal rate, normalized with body weight (M [mg glucose/(min×kg)]).

RESULTS

A total of 30 subjects underwent randomization: one subject in the F/TAF arm withdrew consent after randomization and one in the R/F/TAF arm had to be excluded because of technical failure during HEGC, resulting in 28 subjects in the per-protocol population (F/TAF, n=9 subjects; E/C/F/TAF, n=10 subjects; R/F/TAF n=9 subjects). No significant differences were detected on the baseline characteristics. IR did not differ among the groups before treatment. None of the studied antiretroviral combinations resulted in a significant change in IR after 14 days compared with baseline values, as measured by M (F/TAF, 11.42 ±3.04 mean [±sd] versus 11.43 ±3.23, P=0.49; E/C/F/TAF, 10.04 ±2.49 versus 10.95 ±4.26, P=0.30; R/F/TAF, 11.03 ±1.96 versus 13.01 ±4.11, P=0.13).

CONCLUSIONS

Short-term treatment for F/TAF, E/C/F/TAF or R/F/TAF did not increase IR in healthy male volunteers.

摘要

背景

与特定抗逆转录病毒药物或药物类别相关的胰岛素抵抗（IR）增加是HIV患者发生2型糖尿病的既定危险因素，最终会增加发病率和死亡率。迄今为止，关于基于替诺福韦艾拉酚胺（TAF）方案的IR风险的数据尚不可用。

方法

这项前瞻性随机、开放标签研究评估了IR对30名接受恩曲他滨/替诺福韦艾拉酚胺（F/TAF）、埃替拉韦/考比司他/恩曲他滨/替诺福韦艾拉酚胺（E/C/F/TAF）或利匹韦林/恩曲他滨/替诺福韦艾拉酚胺（R/F/TAF）固定剂量组合（FDCs）的健康志愿者的影响。在14天治疗前后使用高胰岛素-正葡萄糖钳夹技术（HEGC）测量IR。使用平均葡萄糖处置率评估每组IR的变化，并按体重进行标准化（M [mg葡萄糖/（min×kg）]）。

结果

共有30名受试者进行了随机分组：F/TAF组中有1名受试者在随机分组后撤回同意，R/F/TAF组中有1名受试者因HEGC期间技术故障而不得不被排除，导致符合方案人群中有28名受试者（F/TAF组，n = 9名受试者；E/C/F/TAF组，n = 10名受试者；R/F/TAF组，n = 9名受试者）。基线特征未检测到显著差异。治疗前各组之间的IR无差异。与基线值相比，在14天后，通过M测量，所研究的抗逆转录病毒组合均未导致IR发生显著变化（F/TAF组，平均值[±标准差]为11.42±3.04，而11.43±3.23，P = 0.49；E/C/F/TAF组，10.04±2.49，而10.95±4.26，P = 0.30；R/F/TAF组，11.03±1.96，而13.01±4.11，P = 0.13）。