A clinical trial to evaluate the impact of broadly neutralizing antibody VRC01 on HIV viral reservoir and maintenance of suppression in a cohort of early-treated children in Botswana

儿童的双重bNAb治疗研究(“Tatelo”)是一项正在进行的I/II期多点临床试验。 使用两种广中和单抗(BNAbs)VRC01LS和10-1074治疗 感染HIV-1病毒的儿童受到抑制。这项研究正在评估双重bNAbs对维持性疾病的疗效 在病毒抑制的HIV感染儿童中，在缺乏ART的情况下进行病毒抑制 在出生后96小时内(或产中感染后不久)接受抗逆转录病毒治疗。 Tatelo研究中的所有儿童都是从早期婴儿治疗(EIT)研究(U01AI114235)招募的， 从出生起就经常接受临床、病毒学和免疫学评估 特点。接受抗逆转录病毒治疗至少96周并符合病毒学入选标准的儿童被提供 参加Tatelo研究。干预包括两个PK和安全阶段(先是单一阶段，然后是 双bNAbs)，然后进行主要研究干预(双bNAbs加ART至少8周，然后是双 单独使用bNAbs长达24周)，然后是儿童单独接受ART的随访期。 这项研究旨在评估双重bNAb疗法对感染HIV-1的儿童可能带来的三种好处： 1)确定用双bNAb治疗后可维持的病毒学控制持续时间 早期ART，提供概念证明，bNAbs可作为标准ART的可能替代方案 病毒贮备量低的儿童；2)调查bNAb治疗是否与 残留病毒库的大小和/或细胞或克隆组成，这将为 制定策略以限制病毒在儿科的持续时间并破坏病毒库内环境的稳定 患者；以及3)评估bNAbs的治疗是否与定性或定量有关 先天或获得性抗病毒免疫反应的变化，如果它促进了 抗病毒免疫配置文件，可实现自发的治疗后病毒控制。

The Dual bNAb Treatment in Children Study (“Tatelo”) is an ongoing phase I/II, multi-site clinical trial of dual treatment with two broadly neutralizing monoclonal antibodies (bNAbs), VRC01LS and 10-1074, offered to HIV-1 infected virally suppressed children. The study is evaluating the efficacy of dual bNAbs for maintaining viral suppression in the absence of ART among virally suppressed HIV-infected children who started standard ART within 96 hours of birth (or soon after intrapartum infection). All children in the Tatelo Study were recruited from the Early Infant Treatment (EIT) study (U01AI114235), and have been followed from birth with frequent assessments of their clinical, virologic and immunologic characteristics. Children who received at least 96 weeks of ART and met virologic entry criteria were offered enrollment into the Tatelo Study. The intervention consisted of two PK and safety phases (single and then dual bNAbs), followed by the main study intervention (dual bNAbs plus ART for at least 8 weeks, then dual bNAbs alone for up to 24 weeks), and then a follow-up period when children were returned to ART alone. The study is designed to evaluate three possible benefits of dual bNAb therapy in HIV-1-infected children: 1) to determine the duration of virologic control that can be maintained with dual bNAb treatment following early ART, providing proof-of-concept that bNAbs may serve as a possible alternative to standard ART in children with low viral reservoirs; 2) to investigate whether bNAb therapy is associated with changes in the size and/or the cellular or clonal composition of residual viral reservoirs, which will be highly informative for developing strategies to limit viral persistence and to destabilize viral reservoir homeostasis in pediatric patients; and 3) to evaluate whether treatment with bNAbs is associated with qualitative or quantitative changes in innate or adaptive antiviral immune responses, and if it facilitates the development of an antiviral immune profile that can enable spontaneous post-treatment viral control.