University of Oxford, Nuffield Department of Medicine, United Kingdom.
Department of Clinical Research, London School of Hygiene and Tropical Medicine, United Kingdom.
Clin Infect Dis. 2019 Aug 1;69(4):580-587. doi: 10.1093/cid/ciy961.
Older children and adolescents with perinatally acquired human immunodeficiency virus (PHIV) infection in Africa experience multiple comorbidities that are not typical of HIV-associated opportunistic infections, including growth impairment and chronic lung disease. We examined associations between plasma cytomegalovirus (CMV) DNA and lung function and growth.
Plasma CMV DNA loads were measured children aged 6-16 years with PHIV (n = 402) and HIV-uninfected controls (n = 224). The HIV-infected children were either newly diagnosed or known HIV infected and stable on antiretroviral therapy (ART) for >6 months. CMV DNA loads were measured using quantitative polymerase chain reaction. CMV DNAemia was modeled as a time-varying outcome using longitudinal mixed-effects logistic regression.
At enrollment, CMV DNAemia ≥1000 copies/mL (defined as "clinically significant") was detected in 5.8% of uninfected children, 14.7% of HIV-infected participants stable on ART, and 22.6% of HIV-infected ART-naive children (χ2 = 23.8, P < .001). The prevalence of CMV DNAemia ≥1000 copies/mL was associated with CD4 counts <350 cells/µL. Among HIV-infected ART-naive children, the presence of CMV DNAemia of ≥1000 copies/mL was independently associated with reduced lung function (adjusted odds ratio [aOR] = 3.23; 95% confidence interval [CI], 1.23-8.46; P = .017). Among ART-treated children, stunting was associated with CMV DNAemia of ≥1000 copies/mL (aOR = 2.79; 95% CI, 0.97-8.02; P = .057).
Clinically significant levels of CMV DNAemia were common in older children with PHIV, even those on ART, suggesting a role for inadequately controlled CMV infection in the pathogenesis of PHIV comorbidities in Africa.
在非洲,感染了经胎盘获得的人类免疫缺陷病毒(PHIV)的较大儿童和青少年经历了多种非典型的 HIV 相关机会性感染合并症,包括生长受损和慢性肺部疾病。我们研究了血浆巨细胞病毒(CMV)DNA 与肺功能和生长之间的关系。
对 402 名 PHIV 儿童(年龄 6-16 岁)和 224 名 HIV 未感染对照进行了血浆 CMV DNA 载量检测。感染 HIV 的儿童要么是新诊断的,要么是已知 HIV 感染且已稳定接受抗逆转录病毒治疗(ART)>6 个月。使用定量聚合酶链反应(PCR)检测 CMV DNA 载量。CMV DNA 血症作为时间变化的结果,使用纵向混合效应逻辑回归进行建模。
在入组时,未感染儿童中检测到 5.8%存在 CMV DNA 血症≥1000 拷贝/ml(定义为“有临床意义”),稳定接受 ART 的 HIV 感染参与者中为 14.7%,HIV 感染未经 ART 治疗的儿童中为 22.6%(χ2 = 23.8,P <.001)。CMV DNA 血症≥1000 拷贝/ml 的发生率与 CD4 计数<350 个/µL 相关。在未经 ART 治疗的 HIV 感染儿童中,存在 CMV DNA 血症≥1000 拷贝/ml 与肺功能下降独立相关(调整后的优势比[aOR] = 3.23;95%置信区间[CI],1.23-8.46;P =.017)。在接受 ART 治疗的儿童中,生长迟缓与 CMV DNA 血症≥1000 拷贝/ml 相关(aOR = 2.79;95%CI,0.97-8.02;P =.057)。
即使在接受 ART 治疗的情况下,感染了 PHIV 的较大儿童中也普遍存在有临床意义的 CMV DNA 血症,这表明控制不佳的 CMV 感染在非洲 PHIV 合并症的发病机制中起作用。