School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
J Int AIDS Soc. 2020 Jul;23(7):e25580. doi: 10.1002/jia2.25580.
As integrase inhibitors become available in low- and middle-income countries (LMICs), they offer the potential to expand extremely limited treatment options available to children and adolescents. In LMICs, only small numbers have used raltegravir, primarily as part of third-line regimens. Using data from the IeDEA global consortium, we aimed to describe the characteristics of children on raltegravir-containing regimens and their outcomes.
We included data from 1994 to 2017 from children (age <18 years), from East and Southern Africa, Asia and South America, who received cART regimens containing raltegravir for ≥90 days. We describe their characteristics at raltegravir start, and their immunological and virological outcomes.
In total, 62 children were included, with median age at raltegravir initiation of 14.3 years (IQR 11.2 to 15.8) and median CD4 count of 276 cells/µL (IQR 68 to 494). Among 40 (65%) with drug resistance testing prior to raltegravir, 71% were resistant to at least one protease inhibitor (PI), and 32% had high-level resistance to at least one drug class. Most (n = 50; 81%) received raltegravir as part of third-line cART following PI-based regimens, and were on regimens containing four or more drugs (n = 47, 76%). By database closure, median duration on raltegravir was 2.0 years (IQR 0.8 to 3.0), 1 (1.6%) patient had died, 6 (9.7%) were lost to follow-up and 21 (34%) had discontinued raltegravir. Among 15 patients reporting reasons for stopping raltegravir, six discontinued because it was no longer available. Within one year of starting raltegravir, among 53 patients with VL measures, 40 (75%) had VL < 1000 copies/mL, and among 54 with a reported CD4 count, 45 (83%) and 36 (67%) were ≥350 and ≥500 cells/µL, respectively, with median CD4 count increasing to 517.5 cells/µL (IQR 288 to 810).
Among children in LMICs, the initial use of raltegravir has been primarily for post PI-based cART. We found good virological and immunological outcomes despite frequent prior triple-class failure and high levels of drug resistance. Both access to raltegravir and long-term adherence to regimens with large pill-burdens remain challenging. Policies which promote earlier access to new drugs and simplify daily regimens for children and adolescents in LMICs are needed.
随着整合酶抑制剂在中低收入国家（LMICs）的应用，为儿童和青少年提供了有限的治疗选择。在这些国家，只有少数人使用拉替拉韦，主要是作为三线治疗方案的一部分。利用 IeDEA 全球联盟的数据，我们旨在描述接受含拉替拉韦的治疗方案的儿童的特征及其结果。
我们纳入了 1994 年至 2017 年来自东非和南非、亚洲和南美洲年龄<18 岁的儿童（年龄<18 岁），他们接受了含有拉替拉韦的 cART 治疗方案至少 90 天。我们描述了他们在开始使用拉替拉韦时的特征，以及他们的免疫和病毒学结果。
共纳入 62 例患儿，开始使用拉替拉韦时的中位年龄为 14.3 岁（IQR 11.2 至 15.8），中位 CD4 计数为 276 个/μL（IQR 68 至 494）。在 40 例（65%）进行了耐药性检测的患儿中，71%对至少一种蛋白酶抑制剂（PI）耐药，32%对至少一种药物类别有高水平耐药。大多数（n=50；81%）在基于 PI 的方案之后接受拉替拉韦作为三线 cART，并且使用了包含四种或更多药物的方案（n=47，76%）。在数据库关闭时，拉替拉韦的中位使用时间为 2.0 年（IQR 0.8 至 3.0），1 例（1.6%）患者死亡，6 例（9.7%）失访，21 例（34%）停止使用拉替拉韦。在 15 例报告停止使用拉替拉韦的原因的患者中，有 6 例因药物不再供应而停止使用。在开始使用拉替拉韦后的一年内，53 例有病毒载量测量值的患者中，40 例（75%）病毒载量<1000 拷贝/ml，54 例有报告 CD4 计数的患者中，分别有 45 例（83%）和 36 例（67%）的 CD4 计数≥350 和≥500 个/μL，中位 CD4 计数增加至 517.5 个/μL（IQR 288 至 810）。
在中低收入国家的儿童中，拉替拉韦的初始使用主要是在基于 PI 的 cART 之后。尽管先前有过三重耐药和高水平耐药，但我们发现病毒学和免疫学结果良好。获得拉替拉韦和长期坚持儿童和青少年的大剂量药物治疗方案仍然具有挑战性。需要制定促进儿童和青少年获得新药的政策，并简化治疗方案。
