Fougère Yves, Brophy Jason, Hawkes Michael T, Lee Terry, Samson Lindy, Gantt Soren, Dufour Mi-Suk Kang, Renaud Christian, Dieumegard Hinatea, Diallo Madeleine Aby, Canape Jade, Read Stanley, Bitnun Ari, Soudeyns Hugo, Kakkar Fatima
From the Unit of Pediatric Infectious Diseases and Vaccinology, Department of Woman Mother and Child, Lausanne University Hospital, Lausanne, Switzerland.
Centre d'infectiologie mère-enfant (CIME), Centre de recherche Azrieli du CHU Sainte-Justine, Montreal, Quebec, Canada.
Pediatr Infect Dis J. 2025 Apr 3;44(8):764-71. doi: 10.1097/INF.0000000000004811.
Although cytomegalovirus (CMV) disease has been well described among severely immunocompromised children living with HIV (CLWH), the impact of CMV coinfection, is not well understood. The objective of this study was to characterize the clinical and immunologic effects of CMV coinfection in CLWH in Canada.
This is a substudy of the Early Pediatric Initiation, Canada Child Cure Cohort study, which enrolled CLWH in Canada between 2014 and 2018. CMV serostatus was determined at the first (baseline) study visit, and HIV-1 viral load (VL), CMV VL, and lymphocyte subsets were quantified every 3-6 months. For a subset of participants, CD4+ and CD8+ T cell subsets were analyzed using flow cytometry. The clinical outcomes were recorded retrospectively at the baseline visit and prospectively during the study period.
Of the 225 participants, 85.3% were CMV seropositive (CMV+) and 81% had suppressed HIV VL. While there were no significant differences in clinical outcomes between CMV+ and CMV- children, CMV+ children had lower frequencies of CD4+ T cells, higher frequencies of CD8+ T cells, and lower CD4/CD8 ratio at baseline than CMV- children. Children with CMV+ children also demonstrated a higher frequency of CD4+ effector memory cells, lower CD8+ naïve T cells, and higher frequencies of CD8+ terminally differentiated effector memory cells. These differences remained significant even after adjusting for HIV viral control.
CMV coinfection is common among CLWH and is associated with distinct immunological changes despite the effective control of HIV replication with antiretroviral therapy. The long-term implications of these immunological perturbations require further investigation.
尽管巨细胞病毒（CMV）疾病在感染人类免疫缺陷病毒（HIV）的严重免疫功能低下儿童中已有详尽描述，但CMV合并感染的影响尚不明确。本研究的目的是描述加拿大感染HIV儿童中CMV合并感染的临床和免疫学影响。
这是加拿大儿童早期治疗队列研究“早期儿科启动”的一项子研究，该研究于2014年至2018年在加拿大招募了感染HIV的儿童。在首次（基线）研究访视时确定CMV血清状态，每3至6个月对HIV-1病毒载量（VL）、CMV VL和淋巴细胞亚群进行定量分析。对于一部分参与者，使用流式细胞术分析CD4+和CD8+ T细胞亚群。在基线访视时回顾性记录临床结局，并在研究期间前瞻性记录。
在225名参与者中，85.3%为CMV血清阳性（CMV+），81%的HIV VL得到抑制。虽然CMV+和CMV-儿童的临床结局没有显著差异，但CMV+儿童在基线时CD4+ T细胞频率较低，CD8+ T细胞频率较高，CD4/CD8比值低于CMV-儿童。CMV+儿童还表现出较高频率的CD4+效应记忆细胞、较低频率的CD8+初始T细胞以及较高频率的CD8+终末分化效应记忆细胞。即使在调整HIV病毒控制因素后，这些差异仍然显著。
CMV合并感染在感染HIV的儿童中很常见，尽管抗逆转录病毒疗法有效控制了HIV复制，但仍与明显的免疫变化相关。这些免疫紊乱的长期影响需要进一步研究。
