阿根廷因非核苷类逆转录酶抑制剂耐药导致病毒学失败的 HIV 患者中依曲韦林的预测敏感性。

Predicted susceptibility of etravirine in HIV patients experiencing virological failure secondary to non-nucleoside reverse transcriptase inhibitor resistance in Argentina.

机构信息

Hospital Francisco J. Muñiz, Outpatient Care Department, Buenos Aires, Argentina, IDEAA Foundation, Buenos Aires, Argentina.

出版信息

Enferm Infecc Microbiol Clin. 2011 Jun-Jul;29(6):428-31. doi: 10.1016/j.eimc.2011.03.003. Epub 2011 May 17.

DOI:10.1016/j.eimc.2011.03.003

PMID:21592625

Abstract

INTRODUCTION

Virological response to etravirine (ETR) is dependent on the type and number of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs).

METHODS

Data on NNRTI used in HAART at the time of failure and the number of NNRTI-RAMs were collected and retrospectively analyzed. ETR-RAMs were defined as V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S, and M230L, and were analyzed according to the weighted mutation score to predict susceptibility (Vingerhoets 2008).

RESULTS

N=150. Efavirenz (EFV) containing regimen: 76.7%; nevirapine (NVP): 23.3%. Frequency of ETR-RAMs acquired after NNRTI failure: zero=38.7%, one=39.3%, two=17.3%, three=3.3%, four=1.3%. Most frequent ETR-RAMs after failure with EFV: G190A (28.1%), K101E (14.9%), L100I (10.5%); and with NVP: Y181C (41.7%), G190A (30.6%) and A98G (13.9%). Global predicted susceptibility of ETR: highest response: 69.3%, intermediate response: 24.7%, reduced response: 6%. Comparing maximal response with duration of virological failure: EFV-containing regimen: 94.4% (< 24-weeks) vs. 69.8% (>24-weeks) (p=0.02); NVP-containing regimen: 42.9% (< 24-weeks) vs. 56.5% (>24-weeks) (p=0.41). The presence of lamivudine regimen was associated with a better predicted susceptibility (highest response) to ETR (79% vs. 25%; P=.001).

DISCUSSION

The majority of patients maintained susceptibility to ETR after the acquisition of NNRTI resistance. Failing with an EFV-containing regimen had a better predicted susceptibility to ETR than with NVP, especially after short-term virological failure.

摘要

简介

依曲韦林（ETR）的病毒学应答取决于非核苷类逆转录酶抑制剂（NNRTI）耐药相关突变（RAMs）的类型和数量。

方法

收集并回顾性分析了在 HAART 治疗失败时使用的 NNRTI 数据和 NNRTI-RAMs 的数量。将 ETR-RAMs 定义为 V90I、A98G、L100I、K101E/H/P、V106I、E138A、V179D/F/T、Y181C/I/V、G190A/S 和 M230L，并根据加权突变评分分析预测敏感性（Vingerhoets 2008）。

结果

N=150。含依非韦伦（EFV）的方案：76.7%；奈韦拉平（NVP）：23.3%。在 NNRTI 失败后获得 ETR-RAMs 的频率：零=38.7%，一=39.3%，二=17.3%，三=3.3%，四=1.3%。EFV 治疗失败后最常见的 ETR-RAMs：G190A（28.1%）、K101E（14.9%）、L100I（10.5%）；而 NVP 则为 Y181C（41.7%）、G190A（30.6%）和 A98G（13.9%）。ETR 最高预测敏感性：最高反应率为 69.3%，中等反应率为 24.7%，反应率降低为 6%。比较最大反应与病毒学失败持续时间：EFV 含药方案：94.4%（<24 周）与 69.8%（>24 周）（p=0.02）；NVP 含药方案：42.9%（<24 周）与 56.5%（>24 周）（p=0.41）。拉米夫定方案的存在与对 ETR 更高的预测敏感性（最高反应率）相关（79%与 25%；P=.001）。