基于整合酶链转移抑制剂的单片复方治疗方案与卡博特韦+rilpivirine治疗病毒学抑制的HIV感染者时出现的与治疗相关的耐药性突变及因不良事件停药的比较：一项系统文献综述和网状荟萃分析
Comparison of treatment-emergent resistance-associated mutations and discontinuation due to adverse events among integrase strand transfer inhibitor-based single-tablet regimens and cabotegravir + rilpivirine for the treatment of virologically suppressed people with HIV: A systematic literature review and network meta-analysis.
作者信息
Rashid Ishfaq, Unger Nathan R, Willis Connor, Dhippayom Teerapon, Ramgopal Moti, Sherman Elizabeth M, Yared Nicholas, Safran Rachel, Swiatlo Edwin, Weinberg Amy R, Navadeh Soodi, Schmutz Howard Weston, Chaiyakunapruk Nathorn
机构信息
Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, Utah, USA.
Gilead Sciences, Inc., Foster City, California, USA.
出版信息
HIV Med. 2025 Aug;26(8):1184-1198. doi: 10.1111/hiv.70050. Epub 2025 May 27.
OBJECTIVE
This study evaluated rates of treatment-emergent resistance-associated mutations (TE-RAMs) and discontinuation due to adverse events (DC-AEs) across integrase strand transfer inhibitor (INSTI)-based single-tablet regimens and injectable cabotegravir + rilpivirine (CAB + RPV) in virologically suppressed people with HIV.
METHODS
A systematic literature review was conducted for phase 2-4 randomized controlled trials with ≥48 weeks of follow-up involving virologically suppressed people with HIV aged ≥12 years and published January 2003-March 2024. A random-effects network meta-analysis estimated comparative rates of TE-RAMs and DC-AEs among regimens at 48 weeks. Risk of bias and strength of evidence were assessed using Cochrane RoB and CINeMA, respectively.
RESULTS
Fourteen (7509 participants) and nine (4656 participants) studies were included in the TE-RAMs and DC-AEs analyses, respectively. No significant differences in rates of TE-RAMs were observed; risk ratios (RRs) for TE-RAMs for bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and CAB + RPV every 4 weeks (Q4W) versus CAB + RPV every 8 weeks (Q8W) were 0.22 (95% CI, 0.02-2.04), 0.22 (95% CI, 0.00-19.85) and 0.40 (95% CI, 0.14-1.09). Compared with CAB + RPV Q4W and Q8W, DC-AEs were significantly lower with B/F/TAF (RR, 0.15 [95% CI, 0.03-0.75] and RR, 0.16 [95% CI, 0.04-0.67], respectively) and DTG/ABC/3TC (RR, 0.05 [95% CI, 0.01-0.48] and RR, 0.05 [95% CI, 0.01-0.46], respectively).
CONCLUSIONS
In virologically suppressed people with HIV, switching to CAB + RPV Q8W yielded a non-significant increased risk of TE-RAMs compared with INSTI-based 2- and 3-drug regimens and CAB + RPV Q4W. Both CAB + RPV Q4W and Q8W had significantly higher risks of DC-AEs than B/F/TAF and DTG/ABC/3TC. Findings highlight the importance of considering both resistance and tolerability when switching regimens.
目的
本研究评估了在病毒学抑制的HIV感染者中，基于整合酶链转移抑制剂（INSTI）的单片复方治疗方案以及注射用卡博特韦+rilpivirine（CAB+RPV）治疗出现的与耐药相关的突变（TE-RAMs）发生率和因不良事件导致的停药率（DC-AEs）。
方法
对2003年1月至2024年3月发表的、随访时间≥48周、涉及年龄≥12岁的病毒学抑制的HIV感染者的2-4期随机对照试验进行系统文献综述。随机效应网络荟萃分析估计了48周时各治疗方案中TE-RAMs和DC-AEs的比较发生率。分别使用Cochrane RoB和CINeMA评估偏倚风险和证据强度。
结果
TE-RAMs分析纳入了14项研究（7509名参与者），DC-AEs分析纳入了9项研究（4656名参与者）。未观察到TE-RAMs发生率的显著差异；比克替拉韦/恩曲他滨/替诺福韦艾拉酚胺（B/F/TAF）、多替拉韦/阿巴卡韦/拉米夫定（DTG/ABC/3TC）以及每4周一次（Q4W）的CAB+RPV与每8周一次（Q8W）的CAB+RPV相比，TE-RAMs的风险比（RRs）分别为0.22（95%CI，0.02-2.04）、0.22（95%CI，0.00-19.85）和0.40（95%CI，0.14-1.09）。与每4周一次和每8周一次的CAB+RPV相比，B/F/TAF的DC-AEs显著更低（RR分别为0.15[95%CI，0.03-0.75]和RR为0.16[95%CI，0.04-0.67]），DTG/ABC/3TC的DC-AEs也显著更低（RR分别为0.05[95%CI，0.01-0.48]和RR为0.05[95%CI，0.01-0.46]）。
结论
在病毒学抑制的HIV感染者中，与基于INSTI的二联和三联治疗方案以及每4周一次的CAB+RPV相比，切换至每8周一次的CAB+RPV导致TE-RAMs风险增加但不显著。每4周一次和每8周一次的CAB+RPV的DC-AEs风险均显著高于B/F/TAF和DTG/ABC/3TC。研究结果凸显了在切换治疗方案时同时考虑耐药性和耐受性的重要性。
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