Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility
Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility
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DOI：
10.3851/imp2926
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发表时间：
2015-01-01
影响因子：
1.2
通讯作者：
Di Giambenedetto, Simona
中科院分区：
文献类型：
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作者：
Fabbiani, Massimiliano;Grima, Pierfrancesco;Di Giambenedetto, Simona
背景：本研究的目的是探讨病毒耐药性和抗逆转录病毒中枢神经系统（CNS）渗透如何影响hiv感染者的认知能力。方法：我们进行了一项多中心横断面研究，招募了接受神经心理学测试的hiv感染患者，并对血浆样本进行了先前的基因型耐药测试。计算每个方案的CNS穿透有效性（CPE）评分和基因型易感性评分（GSS）。然后构建复合评分（CPE-GSS）。采用logistic回归分析探讨认知障碍相关因素。结果：共纳入215例患者。平均CPE为7.1 (95% CI 6.9, 7.3)，其中206例（95.8%）患者显示CPE bb0 = 6。在使用ANRS、HIVDB和REGA规则的受试者中，GSS校正使CPE值分别降低21.4%（平均6.5,95% CI 6.3, 6.7）、26.5%（平均6.4,95% CI 6.1, 6.6）和24.2%（平均6.4,95% CI 6.2, 6.6）。总体而言，66例（30.7%）患者被认为认知受损。CPE与认知功能障碍之间没有明显的关联。然而，较高的GSS-CPE与较低的认知障碍风险相关(CPE-GSS（ANRS）优势比0.75，P=0.022；CPE-GSS（HIVDB）优势比0.77，P=0.038；CPE-GSS（REGA）优势比0.78，P=0.038)。总体而言，CPE-GSS >= 5似乎是每个不同解释系统中最具歧视性的截止值。结论：gss校正后的CPE评分与神经认知表现的相关性优于标准CPE评分。这些结果表明，抗逆转录病毒药物敏感性，除了药物的中枢神经系统渗透，可以在控制艾滋病毒相关的神经认知障碍中发挥作用。
Background: The aim of the study was to explore how viral resistance and antiretroviral central nervous system (CNS) penetration could impact on cognitive performance of HIV-infected patients.Methods: We performed a multicentre cross-sectional study enrolling HIV-infected patients undergoing neuropsychological testing, with a previous genotypic resistance test on plasma samples. CNS penetration-effectiveness (CPE) scores and genotypic susceptibility scores (GSS) were calculated for each regimen. A composite score (CPE-GSS) was then constructed. Factors associated with cognitive impairment were investigated by logistic regression analysis.Results: A total of 215 patients were included. Mean CPE was 7.1 (95% CI 6.9, 7.3) with 206 (95.8%) patients showing a CPE >= 6. GSS correction decreased the CPE value in 21.4% (mean 6.5, 95% CI 6.3, 6.7), 26.5% (mean 6.4, 95% CI 6.1, 6.6) and 24.2% (mean 6.4, 95% CI 6.2, 6.6) of subjects using ANRS, HIVDB and REGA rules, respectively. Overall, 66 (30.7%) patients were considered cognitively impaired. No significant association could be demonstrated between CPE and cognitive impairment. However, higher GSS-CPE was associated with a lower risk of cognitive impairment (CPE-GSS(ANRS) odds ratio 0.75, P=0.022; CPE-GSS(HIVDB) odds ratio 0.77, P=0.038; CPE-GSS(REGA) odds ratio 0.78, P=0.038). Overall, a cutoff of CPE-GSS >= 5 seemed the most discriminatory according to each different interpretation system.Conclusions: GSS-corrected CPE score showed a better correlation with neurocognitive performance than the standard CPE score. These results suggest that antiretroviral drug susceptibility, besides drug CNS penetration, can play a role in the control of HIV-associated neurocognitive disorders.