Gallien S, Massetti M, Flandre P, Leleu H, Descamps D, Lazaro E
Henri Mondor University Hospital, Créteil, France.
University of Paris-Est Créteil Val de Marne Medical School, Créteil, France.
HIV Med. 2018 Jul 13. doi: 10.1111/hiv.12643.
To compare nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-sparing regimens with tenofovir alafenamide (TAF)-based combinations in HIV-1-infected adults, we performed a network meta-analysis (NMA) to provide estimates of relative efficacy for these two regimens.
A systematic literature review (SLR) was performed to identify phase 3/4 randomized controlled clinical trials evaluating the efficacy of commonly used combination antiretroviral therapy (cART) including an NRTI backbone or that of commonly used NRTI-sparing regimens. A Bayesian random-effect model was used to compare virological suppression rates at 48 weeks for NRTI-sparing regimens and elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF).
Twenty-three studies in treatment-naïve patients identified by the SLR were included in the NMA, including four studies assessing NRTI-sparing regimens. In treatment-naïve patients, the probability of achieving virological suppression at 48 weeks was between 40% and 60% higher with E/C/F/TAF than with NRTI-sparing strategies. The credible interval vs. darunavir/ritonavir (DVR/r) + raltegravir (RAL) and LPV/r monotherapy did not include 1. In the subgroup of naïve patients with viral load < 100 000 HIV-1 RNA copies/mL, a credible difference was found between NRTI-sparing treatments and E/C/F/TAF. Studies in treatment-experienced patients were too heterogeneous to allow for an NMA.
The NMA results suggest that E/C/F/TAF represents a more effective option than NRTI-sparing regimens in terms of 48-week efficacy in treatment-naïve patients. Furthermore, TAF pharmacological properties, as well as tolerability results in clinical studies, suggest a safety profile similar to that of NRTI-sparing regimens. Thus, the E/C/F/TAF combination might represent a more appropriate option than NRTI-sparing regimens for initiation of antiretroviral therapy in treatment-naïve HIV-infected patients.
为比较核苷/核苷酸逆转录酶抑制剂（NRTI）简化治疗方案与基于替诺福韦艾拉酚胺（TAF）的联合治疗方案在HIV-1感染成人中的疗效，我们进行了一项网状荟萃分析（NMA），以评估这两种治疗方案的相对疗效。
进行了一项系统文献综述（SLR），以确定评估常用联合抗逆转录病毒疗法（cART）疗效的3/4期随机对照临床试验，这些cART包括一个NRTI主干方案或常用的NRTI简化治疗方案。采用贝叶斯随机效应模型比较NRTI简化治疗方案与埃替拉韦/考比司他/恩曲他滨/TAF（E/C/F/TAF）在48周时的病毒学抑制率。
SLR确定的23项初治患者研究纳入了NMA，其中包括4项评估NRTI简化治疗方案的研究。在初治患者中，E/C/F/TAF实现48周病毒学抑制的概率比NRTI简化治疗策略高40%至60%。与达芦那韦/利托那韦（DVR/r）+拉替拉韦（RAL）和洛匹那韦/利托那韦（LPV/r）单药治疗相比，可信区间不包括1。在病毒载量<100000 HIV-1 RNA拷贝/mL的初治患者亚组中，NRTI简化治疗与E/C/F/TAF之间存在可信差异。经治患者的研究异质性太大，无法进行NMA。
NMA结果表明，就初治患者的48周疗效而言，E/C/F/TAF比NRTI简化治疗方案是更有效的选择。此外，TAF的药理学特性以及临床研究中的耐受性结果表明其安全性与NRTI简化治疗方案相似。因此，对于初治的HIV感染患者开始抗逆转录病毒治疗，E/C/F/TAF联合治疗可能比NRTI简化治疗方案是更合适的选择。
