HIV感染儿童二线抗逆转录病毒治疗的多中心分析：高失败风险的青少年

Multicentre analysis of second-line antiretroviral treatment in HIV-infected children: adolescents at high risk of failure.

作者信息

Boerma Ragna S, Bunupuradah Torsak, Dow Dorothy, Fokam Joseph, Kariminia Azar, Lehman Dara, Kityo Cissy, Musiime Victor, Palumbo Paul, Schoffelen Annelot, Sophan Sam, Zanoni Brian, Rinke de Wit Tobias F, Calis Job C J, Sigaloff Kim C E

机构信息

Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.

Global Child Health Group, Emma Children's Hospital, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.

出版信息

J Int AIDS Soc. 2017 Sep 15;20(1):21930. doi: 10.7448/IAS.20.1.21930.

DOI:10.7448/IAS.20.1.21930

PMID:28953325

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5640308/

Abstract

INTRODUCTION

The number of HIV-infected children and adolescents requiring second-line antiretroviral treatment (ART) is increasing in low- and middle-income countries (LMIC). However, the effectiveness of paediatric second-line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second-line ART outcomes for children and assessed the need for paediatric third-line ART.

METHODS

We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second-line ART in LMIC, contacting the corresponding study groups and including patient-level data on virologic and clinical outcomes. Kaplan-Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second-line treatment.

RESULTS

We included 12 cohorts representing 928 children on second-line protease inhibitor (PI)-based ART in 14 countries in Asia and sub-Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9-19.4) of children experienced virologic failure. Adolescents (10-18 years) had failure rates of 14.5 (95% CI 11.9-17.6) per 100 person-years compared to 4.5 (95% CI 3.4-5.8) for younger children (3-9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, < 0.001) and short duration of first-line ART before treatment switch (aHR 0.64 and 0.53, = 0.008, for 24-48 months and >48 months, respectively, compared to <24 months).

CONCLUSIONS

In LMIC, paediatric PI-based second-line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI-based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.

摘要

引言

在低收入和中等收入国家（LMIC），需要二线抗逆转录病毒治疗（ART）的艾滋病毒感染儿童和青少年数量正在增加。然而，儿科二线ART的有效性以及病毒学失败的潜在危险因素尚未得到充分描述。我们对儿童二线ART结局进行了汇总分析，并评估了儿科三线ART的需求。

方法

我们通过系统回顾文献进行了一项多中心分析，以确定在LMIC接受二线ART的儿童和青少年队列，联系相应的研究组，并纳入病毒学和临床结局的患者水平数据。使用Kaplan-Meier生存估计和Cox比例风险模型来描述病毒学失败的累积率和预测因素。病毒学失败定义为在二线治疗至少六个月后连续两次病毒载量测量>1000拷贝/ml。

结果

我们纳入了12个队列，代表亚洲和撒哈拉以南非洲14个国家中928名接受基于蛋白酶抑制剂（PI）的二线ART治疗的儿童。24个月后，16.4%（95%置信区间（CI）：13.9-19.4）的儿童出现病毒学失败。青少年（10-18岁）的失败率为每100人年14.5（95%CI 11.9-17.6），而年幼儿童（3-9岁）为4.5（95%CI 3.4-5.8）。病毒学失败的危险因素包括青少年（调整后风险比[aHR] 3.93，<0.001）以及治疗转换前一线ART疗程短（与<24个月相比，24-48个月和>48个月的aHR分别为0.64和0.53，P = 0.008）。