南非（CONNECT）从基于依非韦伦的抗逆转录病毒疗法转向基于多罗替拉韦的抗逆转录病毒疗法后的认知表现、神经精神症状和脑脊液病毒控制：一项前瞻性队列研究。

IF 12.8 1区医学 Q1 IMMUNOLOGY

Lancet Hiv Pub Date : 2024-10-01 Epub Date: 2024-09-13 DOI:10.1016/S2352-3018(24)00209-1

Sam Nightingale, Anna J Dreyer, Kevin G F Thomas, Gert van Zyl, Eric Decloedt, Petrus J W Naude, Catherine Orrell, Phumla Sinxadi, Alan Winston, Saye Khoo, John A Joska

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引用次数: 0

摘要

背景依非韦伦和多罗替拉韦都与神经精神方面的副作用和认知障碍有关。此外，在非洲人群中，尚未对脑脊液（CSF）HIV RNA逸度进行全面研究。我们的目的是研究认知、神经精神症状和 CSF 病毒控制方面的变化，这些变化与从以依非韦伦为基础的抗逆转录病毒疗法（ART）广泛转向以多鲁特韦（Dolutegravir）为基础的抗逆转录病毒疗法（ART）有关：这项针对艾滋病病毒感染者和非艾滋病病毒感染者的前瞻性队列研究从南非开普敦低收入城郊地区的 Gugulethu 社区健康中心招募了成年艾滋病病毒感染者（18-55 岁）。符合条件的参与者已接受以依非韦伦为基础的抗逆转录病毒疗法至少 1 年，并由诊所确定转用以多鲁特韦为基础的抗逆转录病毒疗法，这是国家计划转换的一部分。对参与者进行了基线研究，并在改用多鲁特韦一年后进行了随访。在同一地区招募了未感染艾滋病的患者，他们的年龄和性别均匹配，并在相同的时间间隔内进行了随访。艾滋病病毒感染者和非艾滋病病毒感染者均接受了七个领域的全面认知测试以及功能、情绪、焦虑和睡眠测量。艾滋病病毒感染者进行了脑脊液采样，以进行艾滋病病毒 RNA 定量：从 2019 年 8 月 12 日到 2022 年 9 月 16 日，我们招募了 178 名艾滋病病毒感染者和 95 名非艾滋病病毒感染者。178名艾滋病病毒感染者中的145人（81%）和60名未感染艾滋病病毒者中的40人（66%）接受了随访。基线时，艾滋病病毒感染者的总体认知能力比非艾滋病病毒感染者低 2-57 T 分（p=0-0008）。在随访中，艾滋病病毒感染者认知能力的改善程度高于在非艾滋病病毒感染者中观察到的实践效果（系数 1-40，95% CI 0-48-2-32，p=0-0028），组间认知能力无明显差异（51-43 vs 52-73；p=0-22）。换药后，睡眠质量有所改善（风险比 0-90，95% CI 0-84-0-95；p=0-0002），主要受睡眠紊乱指标的影响。虽然存在基线差异，但抑郁症病例有 9 例。基线时有1例（1%）CSF逸出，随访时有3例（4%）；所有逸出都处于低水平或在重复采样后得到解决：认知和睡眠的改善可能与更换依非韦伦有关。解读：认知和睡眠的改善可能与改用依非韦伦治疗有关，但抑郁症可能会增加，这需要进一步研究。接受多罗替拉韦治疗的非洲病毒抑制型艾滋病患者的认知能力与未感染艾滋病的患者相似。在依非韦伦和多鲁特韦治疗中，CSF逸出都不常见：南非医学研究委员会和英国医学研究委员会，牛顿基金。

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Cognitive performance, neuropsychiatric symptoms, and cerebrospinal fluid viral control following programmatic switch from efavirenz-based to dolutegravir-based antiretroviral therapy in South Africa (CONNECT): a prospective cohort study.

Background: Both efavirenz and dolutegravir have been associated with neuropsychiatric side-effects and cognitive impairment. Furthermore, cerebrospinal fluid (CSF) HIV RNA escape has not been comprehensively studied in African populations. We aimed to examine changes in cognition, neuropsychiatric symptoms, and CSF viral control associated with the widespread switch from efavirenz-based to dolutegravir-based antiretroviral therapy (ART).

Methods: This prospective cohort study of people with HIV and people without HIV recruited adults with HIV (aged 18-55 years) from the Gugulethu Community Health Centre in a low-income periurban area of Cape Town, South Africa. Eligible participants had been receiving efavirenz-based ART for at least 1 year and were identified by the clinic to switch to dolutegravir-based ART as part of the national programmatic switch. Participants were studied at baseline and followed up at 1 year after switch to dolutegravir. People without HIV were recruited from the same area, matched for age and gender, and followed up at the same time interval. People with HIV and people without HIV underwent comprehensive cognitive testing over seven domains and measures of functioning, mood, anxiety, and sleep. People with HIV had CSF sampling for HIV RNA quantification.

Findings: Between Aug 12, 2019, and Sept 16, 2022, we recruited 178 people with HIV and 95 people without HIV. 145 (81%) of 178 people with HIV and 40 (66%) of 60 people without HIV who were offered underwent follow-up. Global cognitive performance was 2·57 T score points lower in people with HIV than in people without HIV at baseline (p=0·0008). At follow-up, cognition in people with HIV improved more than practice effects observed in people without HIV (coefficient 1·40, 95% CI 0·48-2·32, p=0·0028) and no significant difference in cognitive performance between groups was apparent (51·43 vs 52·73; p=0·22). Sleep quality improved following the switch (risk ratio 0·90, 95% CI 0·84-0·95; p=0·0002), driven mainly by indicators of disturbed sleep. There were nine incident cases of depression, although baseline differences were present. There was one case (1%) of CSF escape at baseline and three cases (4%) at follow-up; all were at low levels or resolved with repeated sampling.

Interpretation: Improvements in cognition and sleep are probably related to switching from efavirenz. However, the possible increase in depression warrants further examination. Cognitive performance in virally supressed African people with HIV receiving dolutegravir-based therapy is similar to people without HIV. CSF escape is uncommon on both efavirenz-based and dolutegravir-based therapy.

Funding: South African Medical Research Council and UK Medical Research Council, Newton Fund.

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来源期刊

Lancet Hiv IMMUNOLOGYINFECTIOUS DISEASES&-INFECTIOUS DISEASES

CiteScore

19.90

自引率

4.30%

发文量

368

期刊介绍： The Lancet HIV is an internationally trusted source of clinical, public health, and global health knowledge with an Impact Factor of 16.1. It is dedicated to publishing original research, evidence-based reviews, and insightful features that advocate for change in or illuminates HIV clinical practice. The journal aims to provide a holistic view of the pandemic, covering clinical, epidemiological, and operational disciplines. It publishes content on innovative treatments and the biological research behind them, novel methods of service delivery, and new approaches to confronting HIV/AIDS worldwide. The Lancet HIV publishes various types of content including articles, reviews, comments, correspondences, and viewpoints. It also publishes series that aim to shape and drive positive change in clinical practice and health policy in areas of need in HIV. The journal is indexed by several abstracting and indexing services, including Crossref, Embase, Essential Science Indicators, MEDLINE, PubMed, SCIE and Scopus.