Fairlie Lee, Chernoff Miriam, Cotton Mark F, Bwakura-Dangarembizi Mutsa, Violari Avy, Familiar-Lopez Itziar, Barlow-Mosha Linda, Kamthunzi Portia, McCarthy Katie, Jean-Philippe Patrick, Laughton Barbara, Palumbo Paul E, Boivin Michael J
Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Front Pediatr. 2022 Aug 3;10:899002. doi: 10.3389/fped.2022.899002. eCollection 2022.
The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1104s study evaluated neuropsychological outcomes over 96 weeks in children living with HIV (CLHIV) aged 5-11 years at 6 Sub-Saharan African sites to explore associations between HIV-illness related biomarkers and neuropsychological outcomes.
Children living with HIV had participated in IMPAACT P1060, which compared efficacy of nevirapine versus lopinavir/ritonavir in children initiating ART at <3 years of age. At age 5-11, neuropsychological evaluations of KABC cognitive ability, TOVA attention-impulsivity and BOT-2 motor domains were assessed and repeated after 48 and 96 weeks. Clinical, antiretroviral therapy (ART) and laboratory (immunological and virological) parameters were used to predict neuropsychological outcomes using linear mixed-effects multivariable regression models, controlling for child and caregiver characteristics.
246 CLHIV (45% male, mean age at initial neuropsychological evaluation 7.1 yrs [SD 1.2]) began ART at a median age 14.9 months (IQR 8.2, 25.2). Nadir CD4 percentage was 14.7% (IQR 11.0, 19.5); the median peak viral load (VL) was 750 000 copies/ml (IQR 366 000, 750 000) and 63% had ≥WHO stage 3 clinical disease; 164 (67%) were on lopinavir/ritonavir, 71 (29%) were on nevirapine and 7 (3%) were on efavirenz. Other antiretrovirals were similar. Nevirapine at P1104s study start or later was associated with poorer neuropsychological scores across all domains except Global Executive Composite, even when controlling for nadir CD4 percent and time-varying HIV VL. Other predictors of poorer scores in KABC domains included low birth weight, WHO stage 4 disease and serious illness history and elevated VL was associated with worse BOT-2 scores.
Children receiving nevirapine had poorer neuropsychological scores than those on lopinavir/ritonavir. Antiretroviral choice might adversely impact neuropsychological performance. In addition, low birth weight and markers of severe HIV disease: advanced WHO clinical HIV disease, history of serious illness and an elevated VL, were associated with lower neuropsychological scores.
国际母婴儿科青少年艾滋病临床试验网络（IMPAACT）P1104s研究在撒哈拉以南非洲的6个地点评估了5至11岁感染艾滋病毒儿童（CLHIV）在96周内的神经心理学结果，以探索与艾滋病毒疾病相关生物标志物和神经心理学结果之间的关联。
感染艾滋病毒的儿童参与了IMPAACT P1060研究，该研究比较了奈韦拉平与洛匹那韦/利托那韦在3岁以下开始抗逆转录病毒治疗（ART）儿童中的疗效。在5至11岁时，评估了KABC认知能力、TOVA注意力-冲动性和BOT-2运动领域的神经心理学评估，并在48周和96周后重复评估。使用临床、抗逆转录病毒治疗（ART）和实验室（免疫和病毒学）参数，通过线性混合效应多变量回归模型预测神经心理学结果，同时控制儿童和照顾者的特征。
246名感染艾滋病毒儿童（45%为男性，初次神经心理学评估时的平均年龄为7.1岁[标准差1.2]）在14.9个月（四分位间距8.2，25.2）的中位年龄开始接受抗逆转录病毒治疗。最低CD4百分比为14.7%（四分位间距11.0，19.5）；中位峰值病毒载量（VL）为750000拷贝/ml（四分位间距366000，750000），63%患有≥世界卫生组织3期临床疾病；164名（67%）接受洛匹那韦/利托那韦治疗，71名（29%）接受奈韦拉平治疗，7名（3%）接受依非韦伦治疗。其他抗逆转录病毒药物情况相似。在P1104s研究开始时或之后使用奈韦拉平，与除全球执行综合指标外的所有领域较差的神经心理学评分相关，即使在控制最低CD4百分比和随时间变化的艾滋病毒病毒载量时也是如此。KABC领域较差评分的其他预测因素包括低出生体重、世界卫生组织4期疾病和严重疾病史，病毒载量升高与BOT-2评分较差相关。
接受奈韦拉平治疗的儿童神经心理学评分比接受洛匹那韦/利托那韦治疗的儿童差。抗逆转录病毒药物的选择可能会对神经心理学表现产生不利影响。此外，低出生体重和严重艾滋病毒疾病的标志物：世界卫生组织晚期临床艾滋病毒疾病、严重疾病史和病毒载量升高，与较低的神经心理学评分相关。
