在多次治疗失败的HIV感染患者中，使用阿扎那韦/利托那韦联合替诺福韦进行挽救治疗：随机ANRS 107试验。

Salvage therapy with atazanavir/ritonavir combined to tenofovir in HIV-infected patients with multiple treatment failures: randomized ANRS 107 trial.

作者信息

Piketty Christophe, Gérard Laurence, Chazallon Corine, Marcelin Anne-Geneviève, Clavel François, Taburet Anne-Marie, Calvez Vincent, Madelaine-Chambrin Isabelle, Molina Jean-Michel, Aboulker Jean-Pierre, Girard Pierre-Marie

机构信息

Department of Immunology, Hôpital Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.

出版信息

Antivir Ther. 2006;11(2):213-21.

PMID:16640102

Abstract

BACKGROUND

Ritonavir (RTV)-boosted atazanavir (ATV) and tenofovir disoproxil fumarate (TDF-DF) are promising in highly experienced patients because of their pharmacokinetic profile, activity, safety and resistance properties.

METHODS

A 26-week study of the safety and efficacy of RTV-boosted ATV plus TDF-DF was conducted in 53 HIV-infected patients who were failing their current highly active antiretroviral therapy (HAART) regimen. Patients with history of failure to at least two protease inhibitors (PIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) were randomized to either continue their current regimen (group 1) or replace the PI by ATV (300 mg once daily) boosted by RTV (100 mg; group 2) for 2 weeks. Then, all patients received the same combination of ATV, RTV and TDF-DF (300 mg) plus optimized NRTIs regimen.

RESULTS

At baseline, median CD4+ T-cell count was 206/mm3, median viral load (VL) 5.0 log10/ml and median numbers of NRTI, NNRTI and PI resistance mutations were 7, 1 and 8, respectively. At week 2, median VL remained unchanged from baseline in group 2 as compared with group 1 (-0.1 vs -0.1 log10/ml). At week 26, a mild decrease in median VL from baseline of 0.2 log10/ml was observed, with 16 (31%) and 9 (17%) patients exhibiting a decrease in viral load of at least 0.5 and 1.0 log10/ml, respectively. Baseline phenotypic and genotypic resistance to ATV were the most predictive independent factors of virological response. The regimen was well tolerated.

CONCLUSION

In these very advanced patients failing highly HAART, the combination of boosted ATV plus TDF-DF yielded low antiretroviral activity.

摘要

背景

利托那韦（RTV）增强的阿扎那韦（ATV）和替诺福韦酯富马酸盐（TDF-DF）因其药代动力学特征、活性、安全性和耐药特性，在经验丰富的患者中具有良好前景。

方法

对53例当前高效抗逆转录病毒治疗（HAART）方案失败的HIV感染患者进行了一项为期26周的关于RTV增强的ATV联合TDF-DF安全性和有效性的研究。对至少两种蛋白酶抑制剂（PI）和一种非核苷类逆转录酶抑制剂（NNRTI）治疗失败的患者，随机分为继续当前方案组（第1组）或用RTV（100mg）增强的ATV（每日一次300mg）替代PI组（第2组），为期2周。然后，所有患者接受相同的ATV、RTV和TDF-DF（300mg）联合优化的核苷类逆转录酶抑制剂方案。

结果

基线时，CD4 + T细胞计数中位数为206/mm³，病毒载量（VL）中位数为5.0 log₁₀/ml，核苷类逆转录酶抑制剂、非核苷类逆转录酶抑制剂和蛋白酶抑制剂耐药突变的中位数分别为7、1和8。在第2周时，与第1组相比，第2组的VL中位数与基线相比无变化（-0.1对-0.1 log₁₀/ml）。在第26周时，观察到VL中位数较基线轻度下降0.2 log₁₀/ml，分别有16例（31%）和9例（17%）患者的病毒载量下降至少0.5和1.0 log₁₀/ml。对ATV的基线表型和基因型耐药是病毒学反应最具预测性的独立因素。该方案耐受性良好。