A Phase-IV Non-interventional Study to Assess Virological Effectiveness, Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1 Infected Indian Persons Living with HIV.

IF 0.8 4区 医学 Q4 IMMUNOLOGY
Kuldeep K Ashta, Sumit Arora, Rajesh Khanna, Nishant Raman, Anirudh Anilkumar, Charu Mohan
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引用次数: 0

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

评估基于 DTG 的抗逆转录病毒疗法对印度 HIV-1 感染者的病毒有效性、安全性和耐受性的第四阶段非干预性研究。
背景:多罗替拉韦(DTG)是一种新型的艾滋病病毒感染者(PLH)首选的一线和二线治疗方法。由于最近才推出,基于 DTG 的治疗方案尚未在相当规模的印度人群中就其实际使用情况和安全性进行全面、系统的评估:本研究旨在评估基于 DTG 的抗逆转录病毒疗法(ART)的 24 周免疫免疫结果、人体测量和代谢变化、耐受性和不良事件(AEs):这是一项单中心第四阶段非干预性观察研究,共有322名抗逆转录病毒疗法初试者和治疗经验丰富的PLH在2022年10月之前开始接受以DTG为基础的治疗方案,研究人员对他们进行了为期24周的随访:结果:24周时,新药组所有PLH(n=113)、一线替代组所有PLH(n=67)、一线失败组93.9%PLH(n=46)和二线替代组95.7%PLH(n=89)血浆HIV-RNA病毒学抑制:我们从一个庞大的印度队列中得出的结果表明,病毒学和新陈代谢反应良好,24 周后对基于 DTG 的抗逆转录病毒疗法的耐受性良好。
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来源期刊
Current HIV Research
Current HIV Research 医学-病毒学
CiteScore
1.90
自引率
10.00%
发文量
81
审稿时长
6-12 weeks
期刊介绍: Current HIV Research covers all the latest and outstanding developments of HIV research by publishing original research, review articles and guest edited thematic issues. The novel pioneering work in the basic and clinical fields on all areas of HIV research covers: virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Periodically, the journal invites guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.
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