Department of Medicine, Command Hospital Lucknow, 226002, India.
Department of Medicine, Army College of Medical Sciences, New Delhi, 110010, India.
Curr HIV Res. 2024;22(1):31-46. doi: 10.2174/011570162X264021231108010324.
Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population.
This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens.
A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks.
At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected.
Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.
多替拉韦（DTG）是一种新型的、首选的一线和二线抗人类免疫缺陷病毒（HIV）治疗药物。由于其最近推出，基于 DTG 的方案尚未在相当大的印度人群中进行全面、系统的评估，以了解其真实世界的使用情况和安全性概况。
本研究旨在评估基于 DTG 的抗逆转录病毒（ART）方案在 24 周时的免疫病毒学结果、人体测量学和代谢变化、耐受性和不良事件（AE）。
这是一项单中心、四期、非干预性观察性研究，纳入了 2022 年 10 月前开始使用基于 DTG 的方案的 322 名初治和治疗经验丰富的 HIV 感染者（PLH），并在 24 周时随访结局。
在 24 周时，所有初治组的 PLH（n=113）、所有一线替代组的 PLH（n=67）、所有一线失败组的 93.9%（n=46）和所有二线替代组的 95.7%（n=89）PLH 均达到血浆 HIV-RNA<1000 拷贝/ml 的病毒学抑制。在作为一线或二线 ART 接受 DTG 的 PLH 中，病毒学抑制率到血浆 HIV-RNA<200 拷贝/ml 和<50 拷贝/ml 是一致的。在基线时健康状况较差（HIV-RNA≥1000 拷贝/ml 或 CD4 细胞计数<350 个/μL）的 PLH 中，观察到的平均未调整体重增加为 3.5 公斤（SE：0.330），且差异具有统计学意义。总体而言，27.3%（n=88）的 PLH 体重增加了≥10%基线体重，相当于 3.7%（n=12）出现治疗后新发临床肥胖。DTG 对血脂具有总体中性作用，在从非核苷类逆转录酶抑制剂（NNRTI）或利托那韦增效蛋白酶抑制剂（b/PI）转换的 PLH 中观察到有利的作用，特别是在血脂异常的预处理 PLH 中（总胆固醇中位数变化：28.5mg/dL 和甘油三酯：51mg/dL），可能源自有问题的 ART 的停用。DTG 特异性 AE，包括中枢神经系统 AE 的发生率较低。两名 PLH 发生了近端肌病，一名发生了转氨血症，需要停用 DTG。25.2%（n=27）和 3.2%（n=10）的 PLH 分别出现无症状血清肌酸激酶升高和药物性转氨血症。未检测到肾功能的明显负面影响。
我们在一个大型印度队列中的结果表明，基于 DTG 的 ART 在 24 周时具有良好的病毒学和代谢反应，且具有良好的耐受性。
