Mugusi Sabina, Ngaimisi Eliford, Janabi Mohammed, Mugusi Ferdinand, Minzi Omary, Aris Eric, Bakari Muhammad, Bertilsson Leif, Burhenne Juergen, Sandstrom Eric, Aklillu Eleni
Department of Clinical Pharmacology, School of Medicine, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.
Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Eur J Clin Pharmacol. 2018 Nov;74(11):1405-1415. doi: 10.1007/s00228-018-2499-0. Epub 2018 Jul 12.
Efavirenz-based combination antiretroviral therapy (cART) is associated with neuropsychiatric adverse events. We investigated the time to onset, duration, clinical implications, impact of pharmacogenetic variations, and anti-tuberculosis co-treatment on efavirenz-associated neuropsychiatric manifestations.
Prospective cohort study of cART naïve HIV patients with or without tuberculosis (HIV-TB) co-infection treated with efavirenz-based cART. Rifampicin-based anti-tuberculosis therapy was initiated 4 weeks prior to efavirenz-based cART in HIV-TB patients. Data on demographic, clinical, laboratory, and a 29-item questionnaire on neuropsychiatric manifestations were collected for 16 weeks after cART initiation. Genotyping for CYP2B6, CYP3A5, SLCO1B1, and ABCB1 and quantification of efavirenz plasma concentration were done on the 4th and 16th week.
Data from 458 patients (243 HIV-only and 215 HIV-TB) were analyzed. Overall incidence of neuropsychiatric manifestations was 57.6% being higher in HIV-only (66.7%) compared to HIV-TB patients (47.4%) (p < 0.01). HIV-only patients were more symptomatic, with proportionately higher grades of manifestations compared to HIV-TB patients. Median time to manifestations was 1 week after cART initiation in HIV-only and 6 weeks after anti-TB (i.e., 2 weeks after cART initiation) in HIV-TB patients. HIV-only patients had significantly higher efavirenz plasma concentrations at 4 weeks after cART compared to HIV-TB patients. No association of sex or genotype was seen in relation to neuropsychiatric manifestations. Risk for neuropsychiatric manifestations was three times more in HIV-only patients compared to HIV-TB (p < 0.01).
Incidence of neuropsychiatric manifestations during early initiation of efavirenz-based cART is high in Tanzanian HIV patients. Risk of neuropsychiatric manifestations is lower in HIV patients co-treated with rifampicin containing anti-TB compared to those treated with efavirenz-based cART only.
基于依非韦伦的联合抗逆转录病毒疗法（cART）与神经精神不良事件相关。我们研究了依非韦伦相关神经精神表现的发病时间、持续时间、临床意义、药物遗传学变异的影响以及抗结核联合治疗的影响。
对未接受过cART治疗的HIV患者（无论是否合并结核感染[HIV-TB]）进行前瞻性队列研究，这些患者接受基于依非韦伦的cART治疗。在HIV-TB患者中，基于利福平的抗结核治疗在基于依非韦伦的cART开始前4周启动。在cART开始后16周收集人口统计学、临床、实验室数据以及一份关于神经精神表现的29项问卷。在第4周和第16周进行CYP2B6、CYP3A5、SLCO1B1和ABCB1基因分型以及依非韦伦血浆浓度定量。
分析了458例患者的数据（243例仅感染HIV者和215例HIV-TB患者）。神经精神表现的总体发生率为57.6%，仅感染HIV者（66.7%）高于HIV-TB患者（47.4%）（p<0.01）。仅感染HIV者症状更明显，与HIV-TB患者相比，表现分级比例更高。仅感染HIV者在cART开始后1周出现表现，HIV-TB患者在抗结核治疗后6周（即cART开始后2周）出现表现。与HIV-TB患者相比，仅感染HIV者在cART后4周时依非韦伦血浆浓度显著更高。未发现神经精神表现与性别或基因型有关。仅感染HIV者出现神经精神表现的风险是HIV-TB患者的三倍（p<0.01）。
在坦桑尼亚HIV患者中，早期开始基于依非韦伦的cART时神经精神表现的发生率很高。与仅接受基于依非韦伦的cART治疗的HIV患者相比，接受含利福平抗结核联合治疗的HIV患者出现神经精神表现的风险更低。
