Masquelier B, Assoumou K L, Descamps D, Bocket L, Cottalorda J, Ruffault A, Marcelin A G, Morand-Joubert L, Tamalet C, Charpentier C, Peytavin G, Antoun Z, Brun-Vézinet F, Costagliola D
Laboratoire de Virologie, CHU de Bordeaux and EA 2968, Université Victor Segalen, Bordeaux, France.
J Antimicrob Chemother. 2008 Jun;61(6):1362-8. doi: 10.1093/jac/dkn127. Epub 2008 Apr 4.
We developed clinically relevant genotypic scores for resistance to fosamprenavir/ritonavir in HIV-1 protease inhibitor (PI)-experienced patients.
PI-experienced patients with virological failure receiving fosamprenavir/ritonavir as the sole PI for at least 3 months and with detectable fosamprenavir plasma levels were included. The impact of baseline protease mutations on virological response (VR, i.e. decrease in plasma HIV-1 RNA between baseline and month 3) was analysed using the Mann-Whitney test. Mutations with prevalence >10% and P value <0.10 were retained. The Jonckheere-Terpstra test was used to select the combination of mutations most strongly associated with VR. The association between score and VR was assessed by multivariate backward regression.
In the 73 patients included, the median baseline HIV-1 RNA was 4.6 log(10) copies/mL (range: 2.7-6.9) and the mean decrease at month 3 was -1.07 +/- 1.40 log(10) copies/mL. Ninety per cent of the patients were infected by HIV-1 subtype B variants. Two fosamprenavir/ritonavir mutation scores were constructed: score A (L10F/I/V + L33F + M36I + I54L/M/V/A/T/S + I62V + V82A/F/C/G + I84V + L90M) was based only on mutations associated with a worse VR, whereas score B (L10FIV + L33F + M36I + I54L/M/V/A/T/S + A71V - V77I - N88S + L90M) also took into account favourable mutations. Both scores were independent predictors of VR, however, co-administration of tenofovir was associated with a worse VR and the presence of the N88S protease mutation and co-administration of enfuvirtide with a better VR.
These clinically validated mutation scores should be of interest for the clinical management of PI-experienced patients. The fosamprenavir/ritonavir score A was introduced in the 2006 ANRS algorithm along with isolated mutations I50V and V32I + I47V.
我们为曾接受过HIV-1蛋白酶抑制剂（PI）治疗的患者开发了与临床相关的对福沙普那韦/利托那韦耐药的基因型评分。
纳入曾接受PI治疗且出现病毒学失败、将福沙普那韦/利托那韦作为唯一PI使用至少3个月且血浆福沙普那韦水平可检测的患者。使用Mann-Whitney检验分析基线蛋白酶突变对病毒学反应（VR，即基线至第3个月时血浆HIV-1 RNA的下降）的影响。保留患病率>10%且P值<0.10的突变。使用Jonckheere-Terpstra检验选择与VR关联最强的突变组合。通过多变量向后回归评估评分与VR之间的关联。
纳入的73例患者中，基线HIV-1 RNA中位数为4.6 log(10)拷贝/mL（范围：2.7 - 6.9），第3个月时平均下降-1.07 ± 1.40 log(10)拷贝/mL。90%的患者感染HIV-1 B亚型变体。构建了两个福沙普那韦/利托那韦突变评分：评分A（L10F/I/V + L33F + M36I + I54L/M/V/A/T/S + I62V + V82A/F/C/G + I84V + L90M）仅基于与较差VR相关的突变，而评分B（L10FIV + L33F + M36I + I54L/M/V/A/T/S + A71V - V77I - N88S + L90M）还考虑了有利突变。两个评分均为VR的独立预测因素，然而，替诺福韦的联合使用与较差的VR相关，N88S蛋白酶突变的存在以及恩夫韦肽的联合使用与较好的VR相关。
这些经过临床验证的突变评分对于曾接受PI治疗患者的临床管理应具有重要意义。福沙普那韦/利托那韦评分A与孤立突变I50V以及V32I + I47V一起被纳入2006年法国国家艾滋病研究机构（ANRS）算法。
