Infectious Diseases and AIDS Unit, Hospital Clinic, Barcelona.
Infectious Diseases Unit, Hospital General Universitario de Valencia, Valencia.
AIDS Rev. 2024;26(2):67-79. doi: 10.24875/AIDSRev.24000011.
We describe and analyze resistance-associated mutations (RM) and virological failures (VF) on antiretroviral therapy using the latest approved integrase inhibitors (INIs) dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB), together with their companion drugs in fixed-dose formulations: BIC/emtricitabine/tenofovir; CAB/rilpivirine; DTG/abacavir/lamivudine; DTG/emtricitabine/tenofovir; and DTG/lamivudine. Systematic literature searches were conducted in PubMed and other electronic databases for clinical studies published between January 2010 and May 2023, according to preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA), which analyzed VFs and RMs of INIs. Fifty clinical studies were included in the synthesis. VF in antiretroviral treatment (ART)-naïve patients occurred in 0.7-4.0%, 0.6-1.4%, and 0.6-9.0% of patients treated with DTG, BIC, and CAB, respectively. VF was reported in patients with previous ART in 0-8.1%, 0-2.0%, and 0.4-2.3% of those treated with DTG, BIC, and CAB, respectively. RMs were detected in ART-naïve patients in only one study with DTG (0.3%), none of the studies with BIC, and three of the studies with CAB (0.1-5.4%). In ART-experienced patients, RMs were detected in 0-1.9% of DTG-treated patients. No cases of RM were detected in the 11 BIC studies reviewed. In the case of CAB, RMs were detected in eight studies, ranging from 0.3% to 1.9% of patients. In conclusion, RM rates in the studies reviewed were generally low using the latest INIs. This review identified BIC as the INI with the lowest number of observed VF and lack of RM.
我们描述并分析了使用最新批准的整合酶抑制剂（INIs）多替拉韦（DTG）、比克替拉韦（BIC）和卡替拉韦（CAB）及其固定剂量配方的伴随药物（BIC/恩曲他滨/替诺福韦；CAB/利匹韦林；DTG/阿巴卡韦/拉米夫定；DTG/恩曲他滨/替诺福韦；以及 DTG/拉米夫定）治疗中的耐药相关突变（RM）和病毒学失败（VF）。根据系统评价和荟萃分析的首选报告项目（PRISMA），我们在 PubMed 和其他电子数据库中进行了系统文献检索，以分析 INI 的 VF 和 RM。共纳入 50 项临床研究。在未接受过抗逆转录病毒治疗（ART）的患者中，接受 DTG、BIC 和 CAB 治疗的患者中 VF 的发生率分别为 0.7-4.0%、0.6-1.4%和 0.6-9.0%。在有既往 ART 史的患者中，接受 DTG、BIC 和 CAB 治疗的患者中 VF 的发生率分别为 0-8.1%、0-2.0%和 0.4-2.3%。在仅一项 DTG 研究中发现了未接受过 ART 的患者的 RM（0.3%），在所有 BIC 研究中均未发现 RM，在 3 项 CAB 研究中有 RM（0.1-5.4%）。在有 ART 治疗史的患者中，DTG 治疗组有 0-1.9%的患者出现 RM。在回顾的 11 项 BIC 研究中均未发现 RM 病例。在 CAB 方面，在 8 项研究中检测到 RM，患者比例为 0.3%-1.9%。总之，使用最新的 INIs，研究中 RM 的发生率通常较低。本综述确定 BIC 是 VF 发生率最低且无 RM 的 INI。
