Lao Xiaojie, Zhang Hanxi, Yan Liting, Zhao Hongxin, Zhao Qingxia, Lu Hongyan, Chen Yuewu, Li Huiqin, Chen Jinfeng, Ye Fuxiu, Yu Fengting, Xiao Qing, Li Qun, Liang Xuelei, Yang Xiaojie, Yan Chang, Zhang Fujie
Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
WHO Collaborating Centre for Comprehensive Management of HIV Treatment and Care, Beijing Ditan Hospital Capital Medical University, Beijing, China.
Front Med (Lausanne). 2023 Dec 22;10:1313734. doi: 10.3389/fmed.2023.1313734. eCollection 2023.
Antiretroviral Therapy (ART) in children remains challenging due to resource-constrained settings. We conducted a 13-year, prospective, multicenter cohort study on the effectiveness and safety of LPV/r-based regimens in ART-naive and ART-experienced children.
From January 2008 to May 2021, children living with HIV-1 were recruited with LPV/r-based regimens from 8 clinical research sites in 6 provinces in China. Effectiveness outcomes were virologic failure (defined as at least two consecutive measurements of VL > 200 copies/mL after 6 months of ART) and immune response (defined as CD4% recovered to more than 25% after 12 months of treatment). The safety outcomes were treatment-related grade 2-4 adverse events and abnormal laboratory test results.
A total of 345 ART-naïve children and 113 ART-experienced children were included in this cohort study. The median follow-up time was 7.3 (IQR 5.5-10.5) years. The incidence density of virologic failure was 4.1 (95% CI 3.3-4.9) per 100 person-years in ART-naïve children and 5.0 (95% CI 3.5-6.5) per 100 person-years in ART-experienced children. Kaplan Meyer (KM) curve analysis showed children with ART experience were at a higher risk of virologic failure ( < 0.05). The risk factors of virologic failure in ART-naïve children were clinic setting in rural hospitals (aHR = 2.251, 1.108-4.575), annual missed dose times >5 days of LPV intake (aHR = 1.889, 1.004-3.554); The risk factor of virologic failure in ART-experienced children was missed dose times >5 days (aHR = 2.689, 1.299-5.604) and mother as caregivers for ART administration (aHR = 0.475, 0.238-0.948). However, during long-term treatment, viral suppression rates between ART-naïve and ART-experienced children remained similar. No significant differences were observed in the immune response, treatment-related grade 2-4 events, and abnormal laboratory test results between ART-naïve children and ART-experienced children.
Our research underscores that with consistent, long-term treatment of LPV/r-based regimens, ART-experienced children can achieve therapeutic outcomes comparable to ART-naïve children. It provides crucial insights on LPV/r-based regimens in pediatric HIV treatment, especially in resource-limited settings where high-cost Integrase Strand Transfer Inhibitors (INSTs) are inaccessible. This evidence-based understanding provides an essential addition to the global therapeutic strategies for pediatric HIV treatment.
由于资源受限，儿童抗逆转录病毒疗法（ART）仍然具有挑战性。我们开展了一项为期13年的前瞻性多中心队列研究，以评估基于洛匹那韦/利托那韦（LPV/r）的治疗方案在初治和经治儿童中的有效性和安全性。
2008年1月至2021年5月，来自中国6个省份8个临床研究地点的HIV-1感染儿童采用基于LPV/r的治疗方案入组。有效性结局为病毒学失败（定义为ART治疗6个月后至少连续两次测量病毒载量[VL]＞200拷贝/mL）和免疫反应（定义为治疗12个月后CD4%恢复至25%以上）。安全性结局为治疗相关的2-4级不良事件和实验室检查结果异常。
本队列研究共纳入345例初治儿童和113例经治儿童。中位随访时间为7.3（四分位间距5.5-10.5）年。初治儿童病毒学失败的发病密度为每100人年4.1（95%置信区间3.3-4.9），经治儿童为每100人年5.0（95%置信区间3.5-6.5）。Kaplan Meyer（KM）曲线分析显示，有ART治疗史的儿童病毒学失败风险更高（P＜0.05）。初治儿童病毒学失败的危险因素为农村医院的临床环境（调整后风险比[aHR]=2.251，1.108-4.575）、LPV每年漏服天数＞5天（aHR=1.889，1.004-3.554）；经治儿童病毒学失败的危险因素为漏服天数＞5天（aHR=2.689，1.299-5.604）以及母亲作为ART给药的照料者（aHR=0.475，0.238-0.948）。然而，在长期治疗期间，初治和经治儿童的病毒抑制率保持相似。初治儿童和经治儿童在免疫反应、治疗相关的2-4级事件以及实验室检查结果异常方面未观察到显著差异。
我们的研究强调，通过基于LPV/r的治疗方案进行持续、长期治疗，有ART治疗史的儿童可以获得与初治儿童相当的治疗效果。它为基于LPV/r的治疗方案在儿童HIV治疗中的应用提供了关键见解，特别是在无法获得高成本整合酶链转移抑制剂（INSTs）的资源有限环境中。这种基于证据的认识为全球儿童HIV治疗策略增添了重要内容。
