基于拉替拉韦的高效抗逆转录病毒治疗在感染 HIV 1 的儿童和青少年中的强效和持续的抗病毒反应。

Potent and sustained antiviral response of raltegravir-based highly active antiretroviral therapy in HIV type 1-infected children and adolescents.

机构信息

Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

出版信息

Pediatr Infect Dis J. 2012 Mar;31(3):273-7. doi: 10.1097/INF.0b013e31824580e8.

DOI:10.1097/INF.0b013e31824580e8

PMID:22330165

Abstract

BACKGROUND

There are pediatric patients receiving many highly active antiretroviral therapy (HAART) regimens entailing drug resistance mutations that complicate HAART effective therapies.

METHODS

This was a multicenter retrospective study of 19 multidrug-resistant children and adolescents enrolled from July 2007 to October 2009. Patients were nonresponders because no reduction in HIV type 1 (HIV-1) RNA to undetectable levels was observed during their previous antiretroviral treatment history. The long-term effectiveness of raltegravir (RAL)-based salvage therapy was assessed through a longitudinal analysis of immunologic, virologic, and clinical status of the patients.

RESULTS

Median age was 16.0 (15.0-18.0) years. At baseline, median HIV-1 RNA was 10,000 (4.0 log10 copies/mL) (interquartile range [IQR]: 4300-83,000), and median CD4T-cell count was 329 (18.2% cells/μL) (IQR: 175-452). The backbone regimen included at least 1 fully active drug in 17/19 (89%) patients. Median follow-up with HAART including RAL was 80.1 weeks (IQR: 49.4-96.4): 16/19 (84%) exposed for >120 weeks and 6/19 (32%) >100 weeks. After RAL-based therapy, 4/19 (21%) patients achieved HIV-1 RNA <400 copies and 13/17 (68%) reached HIV-1 RNA <50 copies: 6 (32%) within the first month and 7 (37%) within the first 4 months. CD4+ T-cell recovery (70% to 90% of the baseline values) was observed in 17/19 (89%) patients. No deaths, AIDS-defining illnesses, or symptoms of severe intolerance were recorded. Only 2 patients experienced mild-moderate short-term skin rash. Two (11%) patients had sustained and optimum adherence to HAART. No patients showed resistance mutations to RAL after follow-up.

CONCLUSIONS

We observed a sustained antiviral response and improved immunologic indices in multidrug-resistant pediatric patients, most of whom had received RAL as part of salvage regimens with at least 1 fully active drugs.

摘要

背景

有一些儿科患者接受了多种高效抗逆转录病毒治疗（HAART）方案，这些方案涉及耐药突变，使 HAART 的有效治疗复杂化。

方法

这是一项多中心回顾性研究，纳入了 19 名多药耐药的儿童和青少年患者，他们于 2007 年 7 月至 2009 年 10 月入组。这些患者是因为在之前的抗逆转录病毒治疗中未观察到 HIV-1 病毒载量降至不可检测水平而被认为无应答。通过对患者的免疫、病毒学和临床状况进行纵向分析，评估了基于拉替拉韦（RAL）的挽救治疗的长期效果。

结果

中位年龄为 16.0（15.0-18.0）岁。基线时，中位 HIV-1 RNA 为 10,000（4.0 log10 拷贝/ml）（四分位距 [IQR]：4300-83,000），中位 CD4+T 细胞计数为 329（18.2%细胞/μL）（IQR：175-452）。17/19（89%）名患者的基础方案中至少包含 1 种完全有效的药物。包括 RAL 的 HAART 中位随访时间为 80.1 周（IQR：49.4-96.4）：16/19（84%）名患者暴露时间>120 周，6/19（32%）名患者暴露时间>100 周。在基于 RAL 的治疗后，4/19（21%）名患者的 HIV-1 RNA<400 拷贝/ml，13/17（68%）名患者达到 HIV-1 RNA<50 拷贝/ml：6 名（32%）在第一个月内，7 名（37%）在第四个月内。17/19（89%）名患者的 CD4+T 细胞恢复（基线值的 70%至 90%）。未记录到死亡、艾滋病定义性疾病或严重不耐受的症状。仅有 2 名患者出现轻度至中度短期皮疹。2 名（11%）患者对 HAART 有持续和最佳的依从性。随访后，没有患者对 RAL 产生耐药突变。