Program in Molecular Medicine.
Department of Epidemiology and the Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
AIDS. 2020 Jul 1;34(8):1117-1126. doi: 10.1097/QAD.0000000000002525.
This study evaluated HIV-1 antibody levels as predictors of cell-associated HIV-1 DNA levels in perinatally infected (PHIV) children with long-term viral suppression on antiretroviral therapy (ART).
HIV-1 antibody and HIV-1 DNA levels were measured in blood specimens from 61 children and adolescents from the Pediatric HIV/AIDS Cohort Study: Adolescent Master Protocol. Twenty perinatally HIV-1-exposed, uninfected children studied through 2 years served as controls.
HIV-1 IgG antibodies to six HIV-1 proteins were measured by quantitative ELISA; HIV-1 DNA levels were measured by droplet digital PCR.
Among 13 children with viral suppression at less than 1 year, antibodies to gp160 and gp41 were low but stable longitudinally; antibodies to p17, p24, and RT decreased, and antibodies to p31 were low or undetectable. Among 48 children with viral suppression between 1 and 5 years, antibody levels to all six HIV-1 proteins were higher than in children with earlier viral suppression and remained high over time. A receiver operator curve approach identified gp41 and gp160 as useful predictors of HIV-1 DNA less than 10 or less than 100 copies per million PBMC (cpm); C-statistics including all antibodies ranged from 0.75 to 0.77. An ensemble learning approach also identified gp41 and gp160 as important predictors of HIV-1 DNA less than 10 or less than 100 cpm; area under the curve estimates utilizing all HIV-1 antibodies ranged from 0.70 to 0.81.
Quantitative HIV-1 gp41 and gp160 antibody levels may serve as rapid, inexpensive screening tools for low PBMC HIV-1 DNA levels in children with viral suppression on ART, facilitating inclusion into remission protocols.
本研究评估了 HIV-1 抗体水平作为长期接受抗逆转录病毒治疗(ART)的母婴传播感染(PHIV)儿童细胞相关 HIV-1 DNA 水平的预测因子。
对儿科 HIV/AIDS 队列研究:青少年主方案中 61 名儿童和青少年的血液标本进行了 HIV-1 抗体和 HIV-1 DNA 水平检测。20 名母婴 HIV-1 暴露但未感染的儿童在 2 年内作为对照进行研究。
通过定量 ELISA 检测 HIV-1 IgG 抗体针对六种 HIV-1 蛋白;通过液滴数字 PCR 检测 HIV-1 DNA 水平。
在 13 名病毒抑制不到 1 年的儿童中,针对 gp160 和 gp41 的抗体水平较低但纵向稳定;针对 p17、p24 和 RT 的抗体水平下降,针对 p31 的抗体水平较低或无法检测到。在 48 名病毒抑制时间在 1 至 5 年的儿童中,针对所有六种 HIV-1 蛋白的抗体水平均高于病毒抑制更早的儿童,且随着时间的推移保持高水平。接受者操作特征曲线方法确定 gp41 和 gp160 是预测 PBMC 中 HIV-1 DNA 小于 10 或小于 100 拷贝/百万 PBMC(cpm)的有用指标;包括所有抗体的 C 统计量范围为 0.75 至 0.77。基于集合学习的方法也确定了 gp41 和 gp160 是预测 PBMC 中 HIV-1 DNA 小于 10 或小于 100 cpm 的重要指标;利用所有 HIV-1 抗体的曲线下面积估计值范围为 0.70 至 0.81。
定量 HIV-1 gp41 和 gp160 抗体水平可能作为 ART 病毒抑制儿童 PBMC 中 HIV-1 DNA 水平较低的快速、廉价的筛选工具,促进纳入缓解方案。