Departments of Virology and Immunology, Chantal Biya International Reference Centre for Research on HIV/AIDS Prevention and Management (CIRCB), Yaounde, Cameroon; Department of Experimental Medicine, PhD Course in Microbiology, Immunology, Infectious Diseases and Transplants (MIMIT), University of Rome "Tor Vergata", Rome, Italy.
Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.
J Pediatr. 2024 Apr;267:113919. doi: 10.1016/j.jpeds.2024.113919. Epub 2024 Jan 17.
To conduct a comprehensive, systematic review of the profile of HIV-1 reservoirs in children and adolescents with perinatally acquired HIV infection.
Randomized and nonrandomized trials, cohort studies, and cross-sectional studies on HIV reservoirs in pediatric populations, published between 2002 and 2022, were included. Archived-drug resistance mutations (ADRMs) and the size of reservoirs were evaluated. Subgroup analyses were performed to characterize further the data, and the meta-analysis was done through random effect models.
Overall, 49 studies from 17 countries worldwide were included, encompassing 2356 perinatally infected participants (48.83% females). There are limited data on the quantitative characterization of viral reservoirs in sub-Saharan Africa, with sensitive methodologies such as droplet digital polymerase chain reaction rarely employed. The overall prevalence of ADRMs was 37.80% (95% CI 13.89-65.17), with 48.79% (95% CI 0-100) in Africa, 42.08% (95% CI 6.68-82.71) in America, 23.88% (95% CI 14.34-34.90) in Asia, and 20.00% (95% CI 10.72-31.17) in Europe, without any difference between infants and adolescents (P = .656). Starting antiretroviral therapy (ART) before 2 months of age limited the levels of HIV-1 DNA (P = .054). Participants with long-suppressed viremia (>5 years) had lower levels of HIV-1 DNA (P = .027). Pre- and post-ART CD4 ≤29% and pre-ART viremia ≥5Log were all found associated with greater levels of HIV-1 DNA (P = .038, P = .047, and P = .041, respectively).
The pooled prevalence of ADRMs is high in perinatally infected pediatric population, with larger proviral reservoir size driven by delayed ART initiation, a shorter period of viral suppression, and immunovirological failures. Thus, strategies for pediatric HIV functional cure should target children and adolescents with very early ART initiation, immunocompetence, and long-term viral suppression.
全面、系统地综述围生期感染 HIV 的儿童和青少年体内 HIV-1 储存库的特征。
纳入了 2002 年至 2022 年间发表的关于儿科人群 HIV 储存库的随机和非随机试验、队列研究和横断面研究。评估了储存库的耐药突变（ADRMs）和储存库的大小。进行了亚组分析以进一步描述数据，并通过随机效应模型进行了荟萃分析。
来自全球 17 个国家的 49 项研究共纳入了 2356 名围生期感染的参与者（48.83%为女性）。在撒哈拉以南非洲地区，对病毒储存库的定量特征描述数据有限，很少使用敏感的方法，如液滴数字聚合酶链反应。ADRMs 的总体流行率为 37.80%（95%CI 13.89-65.17），非洲为 48.79%（95%CI 0-100），美洲为 42.08%（95%CI 6.68-82.71），亚洲为 23.88%（95%CI 14.34-34.90），欧洲为 20.00%（95%CI 10.72-31.17），婴儿和青少年之间无差异（P=0.656）。在 2 个月龄前开始抗逆转录病毒治疗（ART）可降低 HIV-1 DNA 水平（P=0.054）。病毒载量长期抑制（>5 年）的参与者 HIV-1 DNA 水平较低（P=0.027）。ART 前和 ART 后 CD4≤29%以及 ART 前病毒载量≥5Log 均与 HIV-1 DNA 水平升高相关（P=0.038、P=0.047 和 P=0.041）。
围生期感染的儿科人群中 ADRMs 的总体流行率较高，较大的前病毒储存库大小与延迟 ART 启动、较短的病毒抑制时间和免疫病毒学失败有关。因此，儿科 HIV 功能性治愈的策略应针对早期开始 ART、免疫功能健全和长期病毒抑制的儿童和青少年。
