Division of Infectious Diseases, Georgetown University Medical Center, Washington, District of Columbia, USA.
Department of Neurology and John Hopkins University School of Medicine, Baltimore, Maryland, USA.
AIDS Res Hum Retroviruses. 2022 Jul;38(7):561-570. doi: 10.1089/AID.2021.0097. Epub 2022 Mar 2.
Neurologic complications of the human immunodeficiency virus (HIV) are common in treated individuals, and toxicity of certain antiretroviral therapies (ART) may contribute to cognitive impairment. We investigated exposures to specific ART and cognition among women living with HIV (WLWH). Virologically suppressed (viral load <200 copies/mL during at least two semi-annual visits) WLWH and age/race matched HIV-seronegative controls enrolled in the Women's Interagency HIV Study who completed at least two biennial cognitive assessments were included. Analysis of WLWH was restricted to those with exposure to the drug class of interest and a nucleoside reverse transcriptase inhibitor (NRTI) backbone. Generalized estimating equations were used to evaluate repeated measures of cognition over time in association with ART class exposure. Among 1,242 eligible WLWH, 20% ( = 247) had isolated drug exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI), 18% ( = 219) to protease inhibitors (PIs), and 6% ( = 79) to integrase inhibitors with a NRTI backbone. Cognitive assessments were performed at a median of 3 biennial visits {IQR 2-4 visits}. At the index assessment, 21% of WLWH demonstrated global cognitive impairment versus 29% at their last cognitive assessment. In multivariable analyses adjusted for hypertension, depression, diabetes mellitus, history of AIDS-defining illness, alcohol use, number of medications, and time on ART, WLWH exposed to NNRTIs demonstrated verbal learning improvements (mean T-score change 1.3, = .020) compared to other treated women. Compared to HIV-seronegative women, WLWH exposed to PIs had worse verbal learning (mean T-score difference -2.62, = .002) and verbal memory performance (mean T-score difference -1.74, = .032) at baseline. Compared to HIV-seronegative women, WLWH exposed to PIs had improvements in verbal learning (mean T-score slope difference 0.36, = .025) and verbal memory (mean T-score slope difference 0.32, = .042). The index T-score and slope of change in the T-score were similar among other treated groups and the HIV-seronegative group. We noted emerging trends in cognition in WLWH exposed to specific drug classes. Ongoing study of this relatively young group is important to characterize long-term cognitive outcomes and effect of antiretrovirals as treatment guidelines evolve.
人类免疫缺陷病毒 (HIV) 的神经系统并发症在接受治疗的个体中很常见，某些抗逆转录病毒疗法 (ART) 的毒性可能导致认知障碍。我们研究了特定 ART 暴露与 HIV 阳性女性 (WLWH) 的认知之间的关系。在妇女健康倡议研究中，符合条件的 WLWH 是经过病毒学抑制 (至少两次半年度就诊时病毒载量 <200 拷贝/mL) 且与 HIV 阴性的年龄和种族相匹配的女性，并且完成了至少两次两年一次的认知评估。对 WLWH 的分析仅限于暴露于感兴趣的药物类别和核苷逆转录酶抑制剂 (NRTI) 骨干的女性。使用广义估计方程评估与 ART 类暴露相关的随时间重复的认知测量。在 1242 名符合条件的 WLWH 中，20% ( = 247) 有单独的非核苷逆转录酶抑制剂 (NNRTI) 药物暴露，18% ( = 219) 有蛋白酶抑制剂 (PI) 暴露，6% ( = 79) 有整合酶抑制剂和 NRTI 骨干。认知评估在中位数为 3 次两年一次的就诊中进行 {IQR 2-4 次就诊}。在指数评估时，21%的 WLWH 表现出全球认知障碍，而在最后一次认知评估时为 29%。在调整高血压、抑郁症、糖尿病、艾滋病定义性疾病史、饮酒、用药数量和 ART 时间的多变量分析中，与其他接受治疗的女性相比，NNRTI 暴露的 WLWH 表现出语言学习能力提高 (平均 T 评分变化 1.3， = .020)。与 HIV 阴性女性相比，PI 暴露的 WLWH 在基线时表现出较差的语言学习 (平均 T 评分差异 -2.62， = .002) 和语言记忆表现 (平均 T 评分差异 -1.74， = .032)。与 HIV 阴性女性相比，PI 暴露的 WLWH 的语言学习 (平均 T 评分斜率差异 0.36， = .025) 和语言记忆 (平均 T 评分斜率差异 0.32， = .042) 有所提高。其他治疗组和 HIV 阴性组的 T 评分指数和变化斜率相似。我们注意到在特定药物类别暴露的 WLWH 中认知出现新趋势。随着治疗指南的发展，对这个相对年轻的群体进行持续研究对于描述长期认知结果和抗逆转录病毒的影响非常重要。
