英国/爱尔兰儿童抗逆转录病毒治疗转换后的脂肪萎缩/脂肪肥厚结局。

Lipoatrophy/lipohypertrophy outcomes after antiretroviral therapy switch in children in the UK/Ireland.

机构信息

Family Infectious Diseases Clinical Research Unit (FAMCRU), Stellenbosch University, Cape Town, South Africa.

Department of Paediatrics and Child Health, Tygerberg Children's Hospital and Stellenbosch University, Cape Town, South Africa.

出版信息

PLoS One. 2018 Apr 4;13(4):e0194132. doi: 10.1371/journal.pone.0194132. eCollection 2018.

DOI:10.1371/journal.pone.0194132

PMID:29617438

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5884482/

Abstract

BACKGROUND

Following widespread use of stavudine, a thymidine analogue, in antiretroviral therapy (ART) over the past three decades, up to a third of children developed lipoatrophy (LA) and/or lipohypertrophy (LH). Following phasing-out of stavudine, incidence of newly-diagnosed LA and LH declined dramatically. However, the natural history of existing cases should be explored, particularly with prolonged protease inhibitor exposure.

METHODS

The Collaborative HIV Paediatric Study (CHIPS) is a multicentre cohort study of most HIV-infected children in the United Kingdom and Ireland. Those on ART with a LA/LH assessment recorded in 2003-2011 were included. Assessments were completed annually by consultant physicians. Using the 0-3 grading system, LA or LH was defined as grade 2 or 3. Resolution was defined as return to grade 1 or 0 in all body regions.

RESULTS

Of 1345 children followed for median (IQR) 5.5 (2.9, 8.2) years after ART initiation, 30 developed LA and 27 developed LH, all at least 2 years after ART initiation. Median age at LA diagnosis was 11 (10, 13) years and at LH diagnosis was 13 (11, 15) years. Children with LA were more likely white (p<0.0001); lower height-for-age z-score at ART initiation (p = 0.02); initiated ART earlier (p = 0.04), with longer ART exposure (p = 0.04). Children with LH were similar to those without. Analysis of individual drugs revealed that LA was associated with greater duration of exposure to stavudine and didanosine; while LH was associated with greater duration of exposure to stavudine and ritonavir (given alone or in combination with another protease inhibitor). Median time in follow-up following ART switch was 2.8 (1.9, 4.9) and 2.5 (1.6, 4.7) years respectively. Resolution occurred in 10 (30%) of LA cases (median time to resolution 2.3 [1.8, 3.6] years) and 3 (11%) of LH cases (median time to resolution 2.0 [1.7, 2.1] years).

CONCLUSIONS

Prevalence of LA and LH were low, with some resolution noted, especially for LA. More long-term data are needed.

摘要

背景

在过去的三十年中，由于广泛使用了替诺福韦（一种胸苷类似物）作为抗逆转录病毒疗法（ART）的一部分，多达三分之一的儿童出现了脂肪萎缩（LA）和/或脂肪增生（LH）。随着替诺福韦的逐步淘汰，新诊断的 LA 和 LH 的发病率急剧下降。然而，应该探索现有病例的自然病史，特别是在长期使用蛋白酶抑制剂的情况下。

方法

合作性 HIV 儿科研究（CHIPS）是一项针对英国和爱尔兰大多数 HIV 感染儿童的多中心队列研究。研究纳入了在 2003 年至 2011 年间接受过 ART 治疗并记录了 LA/LH 评估的儿童。评估由顾问医生每年完成。使用 0-3 分级系统，LA 或 LH 定义为 2 级或 3 级。在所有身体区域中，恢复定义为恢复到 1 级或 0 级。

结果

在 ART 开始后中位（IQR）5.5（2.9，8.2）年的 1345 名儿童中，30 名出现 LA，27 名出现 LH，均在 ART 开始后至少 2 年出现。LA 诊断的中位年龄为 11（10，13）岁，LH 诊断的中位年龄为 13（11，15）岁。患有 LA 的儿童更可能是白人（p<0.0001）；在开始 ART 时身高年龄 z 评分较低（p=0.02）；更早开始 ART（p=0.04），接受的 ART 暴露时间更长（p=0.04）。患有 LH 的儿童与没有的儿童相似。对个别药物的分析表明，LA 与更长时间暴露于替诺福韦和去羟肌苷有关；而 LH 与更长时间暴露于替诺福韦和利托那韦（单独使用或与其他蛋白酶抑制剂联合使用）有关。ART 转换后中位随访时间分别为 2.8（1.9，4.9）和 2.5（1.6，4.7）年。LA 病例中有 10 例（30%）（恢复时间中位数为 2.3 [1.8，3.6]年）和 LH 病例中有 3 例（11%）（恢复时间中位数为 2.0 [1.7，2.1]年）出现了恢复。