The Association of Intraocular Efavirenz Concentrations and HIV-1 Viral Load Among Persons With HIV.

IF 2.9 3区 医学 Q3 IMMUNOLOGY JAIDS Journal of Acquired Immune Deficiency Syndromes Pub Date : 2024-07-01 DOI:10.1097/QAI.0000000000003426
Pei Zhang, Yiwen Qian, Luoziyi Wang, Jinshan Suo, Lin Yin, Yuceng Wang, Lijun Zhang, Zhiliang Wang
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Abstract

Objective: Efavirenz (EFV) is commonly used in combination antiretroviral therapy. However, in our previous study, many persons living with HIV exhibited ocular complications despite undergoing effective combination antiretroviral therapy. Here, we aimed to determine the intraocular EFV concentrations in the vitreous and analyze the factors affecting viral load in the vitreous in patients with HIV-associated retinopathies.

Design: Observational, retrospective study.

Methods: Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy were enrolled between January 2019 and August 2022. The patients were divided into 2 groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during pars plana vitrectomy. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using ultra-high-performance liquid chromatography/tandem mass spectrometry.

Results: The median age of the enrolled patients was 48 years (interquartile range, 32.25-53.25), including 12 men and 2 women. Median vitreous and plasma EFV concentrations were 141.5 (interquartile range, 69.63-323.75) and 2620 ng/mL (1680-4207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0.04 vs 0.12, P = 0.042).

Conclusions: The vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be because of poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with RD, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit HIV-1 replication in ocular tissues.

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艾滋病病毒感染者眼内依非韦伦浓度与 HIV-1 病毒载量的关系。
目的:依非韦伦(EFV)是抗逆转录病毒联合疗法(cART)的常用药物。然而,在我们之前的研究中,许多人类免疫缺陷病毒(HIV)感染者尽管接受了有效的 cART 治疗,但仍出现了眼部并发症。在此,我们旨在确定玻璃体内EFV的浓度,并分析影响HIV相关视网膜病变患者玻璃体内病毒载量的因素:观察性、回顾性研究:在2019年1月至2022年8月期间,14名接受EFV联合抗逆转录病毒治疗的患者接受了玻璃体旁切除术(PPV)。根据是否存在视网膜脱离(RD)将患者分为两组。PPV 期间记录了患者特征以及血浆和玻璃体内的 HIV-1 RNA 水平。采用超高效液相色谱/串联质谱法(UHPLC-MS/MS)获取配对血浆和玻璃体样本,进行EFV浓度分析:入组患者的中位年龄为 48 岁(四分位数间距 [IQR],32.25-53.25),其中男性 12 人,女性 2 人。玻璃体和血浆EFV浓度中位数分别为141.5(IQR,69.63-323.75)和2,620纳克/毫升(1,680-4,207.5)。所有参与者配对样本中玻璃体/血浆 EFV 浓度的中位比值为 0.053 (0.018-0.118)。玻璃体/血浆EFV浓度中位数在非RD组和RD组之间存在显著差异(0.04 vs 0.12,p = 0.042)。 结论玻璃体EFV浓度不足以抑制病毒在眼内组织中的复制,这可能是由于对血液-视网膜屏障的穿透力较差。高玻璃体EFV浓度与视网膜脱离有关,表明EFV浓度与血-视网膜屏障破坏的严重程度相关。这意味着 EFV 并非抑制眼组织中 HIV-1 复制的合适抗病毒药物。
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来源期刊
CiteScore
5.80
自引率
5.60%
发文量
490
审稿时长
3-6 weeks
期刊介绍: JAIDS: Journal of Acquired Immune Deficiency Syndromes​ seeks to end the HIV epidemic by presenting important new science across all disciplines that advance our understanding of the biology, treatment and prevention of HIV infection worldwide. JAIDS: Journal of Acquired Immune Deficiency Syndromes is the trusted, interdisciplinary resource for HIV- and AIDS-related information with a strong focus on basic and translational science, clinical science, and epidemiology and prevention. Co-edited by the foremost leaders in clinical virology, molecular biology, and epidemiology, JAIDS publishes vital information on the advances in diagnosis and treatment of HIV infections, as well as the latest research in the development of therapeutics and vaccine approaches. This ground-breaking journal brings together rigorously peer-reviewed articles, reviews of current research, results of clinical trials, and epidemiologic reports from around the world.
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