泰国儿童双核苷逆转录酶抑制剂治疗失败后基因分型的抗逆转录病毒治疗结果。

Antiretroviral treatment outcome following genotyping in Thai children who failed dual nucleoside reverse transcriptase inhibitors.

机构信息

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Center, Bangkok, Thailand.

出版信息

Int J Infect Dis. 2010 Apr;14(4):e311-6. doi: 10.1016/j.ijid.2009.05.017. Epub 2009 Aug 21.

DOI:10.1016/j.ijid.2009.05.017

PMID:19699673

Abstract

OBJECTIVE

To evaluate outcomes in dual nucleoside reverse transcriptase inhibitor (NRTI) pretreated children after genotyping (GT).

METHODS

We assessed CD4 and viral load (VL) in children three years after baseline GT at the time of dual NRTI failure. Baseline high grade resistance (HR) was defined as >or=4 nucleoside analogue mutations (NAMs)+/-Q151M or 69 insertion complex, and low grade resistance (LR) was defined as <4 NAMs. Genotypic susceptibility scores (GSS) were determined. The current selection of antiretrovirals (ARV) was based on physician judgment and ARV availability.

RESULTS

Seventy-two children were enrolled, with a mean age of 9.3 years; 61% were female. Baseline median CD4 was 18%, VL was 1.7 log(10) with HR 37.5%, LR 56.9% and no mutation (NR, no resistance) 5.6%. Sixty-five (90.3%) switched ARV: 46.2% non-nucleoside reverse transcriptase inhibitor (NNRTI), 30.8% protease inhibitor (PI), and 23.1% PI+NNRTI based highly active antiretroviral therapy (HAART). The choice of regimen did not differ based on baseline HR, LR, and NR. The median duration from dual NRTI therapy to HAART was 5.4 years (interquartile range (IQR) 4.0-6.9 years) and the mean (SD) duration of current HAART regimen was 1.51 (1.78) years; both were similar between ARV groups. Five children continued dual NRTI, two interrupted therapy. The GSS score was significantly higher in the PI group (3.1) vs. PI+NNRTI (2.5) vs. NNRTI (2.6) groups. Sixty-three percent of the HR group used PI or PI+NNRTI-based HAART compared to 41% of the LR group, p=not significant. At follow-up, median CD4 changes from baseline were +5% and VL -2.2 log(10) (p<0.001). VL <1.7 log(10) was seen in 59.3% of HR, 58.5% of LR, and 50.0% of NR groups (no significant difference). More children on PI (75%) and PI+NNRTI (80%) based HAART had VL <50 compared to NNRTI-based HAART (50%), p=0.003.

CONCLUSION

PI-based regimens showed a higher rate of undetectable VL compared with NNRTI-based regimens. Having GT may not affect second-line treatment choices in developing countries, most likely due to late VL failure and limited availability of PIs.

摘要

目的

评估基因型（GT）后双重核苷逆转录酶抑制剂（NRTI）预处理儿童的结局。

方法

我们在双重 NRTI 失败时，在基线 GT 后三年评估儿童的 CD4 和病毒载量（VL）。基线高等级耐药（HR）定义为 >或=4 种核苷类似物突变（NAMs）+/-Q151M 或 69 插入复合物，低等级耐药（LR）定义为 <4 NAMs。确定基因型易感性评分（GSS）。目前抗逆转录病毒药物（ARV）的选择基于医生的判断和 ARV 的可获得性。

结果

共纳入 72 名儿童，平均年龄为 9.3 岁；61%为女性。基线中位数 CD4 为 18%，VL 为 1.7 log(10)，HR 为 37.5%，LR 为 56.9%，NR（无耐药）为 5.6%。65 名（90.3%）患儿更换了 ARV：46.2%为非核苷逆转录酶抑制剂（NNRTI），30.8%为蛋白酶抑制剂（PI），23.1%为 PI+NNRTI 高效抗逆转录病毒治疗（HAART）。基线 HR、LR 和 NR 对方案选择无影响。从双重 NRTI 治疗到 HAART 的中位时间为 5.4 年（四分位间距（IQR）4.0-6.9 年），目前 HAART 方案的平均（SD）持续时间为 1.51（1.78）年；各组间均无差异。5 名儿童继续使用双重 NRTI，2 名儿童中断治疗。PI 组的 GSS 评分（3.1）显著高于 PI+NNRTI 组（2.5）和 NNRTI 组（2.6）。HR 组中有 63%使用 PI 或 PI+NNRTI 为基础的 HAART，而 LR 组为 41%，p 值无显著差异。随访时，CD4 中位数较基线变化为+5%，VL-2.2 log(10)（p<0.001）。HR 组中 59.3%、LR 组中 58.5%和 NR 组中 50.0%（无显著差异）的 VL<1.7 log(10)。基于 PI（75%）和 PI+NNRTI（80%）的 HAART 方案中 VL<50 的患儿比例高于基于 NNRTI 的 HAART 方案（50%），p=0.003。