奈韦拉平、司他夫定和拉米夫定通用固定剂量组合用于喀麦隆HIV-1感染成人的有效性和安全性：开放标签多中心试验。

Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial.

作者信息

Laurent Christian, Kouanfack Charles, Koulla-Shiro Sinata, Nkoué Nathalie, Bourgeois Anke, Calmy Alexandra, Lactuock Bernadette, Nzeusseu Viviane, Mougnutou Rose, Peytavin Gilles, Liégeois Florian, Nerrienet Eric, Tardy Michèle, Peeters Martine, Andrieux-Meyer Isabelle, Zekeng Léopold, Kazatchkine Michel, Mpoudi-Ngolé Eitel, Delaporte Eric

机构信息

Institut de Recherche pour le Développement and Department of International Health, University of Montpellier (UMR 145), Montpellier, France.

出版信息

Lancet. 2004;364(9428):29-34. doi: 10.1016/S0140-6736(04)16586-0.

DOI:10.1016/S0140-6736(04)16586-0

PMID:15234853

Abstract

BACKGROUND

Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine.

METHODS

60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis.

FINDINGS

At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per microL (IQR 78-167) and median plasma HIV-1 RNA was 104?736 copies per mL (40804-243787). The proportion of patients with undetectable viral load (<400 copies per mL) after 24 weeks of treatment was 80% (95% CI 68-89). Median (IQR) change in viral load was -3.1 log10 copies per mL (-2.5 to -3.6) and in CD4 count 83 cells per microL (40-178). The probability of remaining alive or free of new AIDS-defining events was 0.85 (95% CI 0.73-0.92). Frequency of disease progression was 32.0 (95% CI 16.6-61.5), severe adverse effects 17.8 (7.4-42.7), and genotypic resistance mutations 7.1 (1.8-28.4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine.

INTERPRETATION

Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.

摘要

背景

通用型固定剂量复方制剂已获得世界卫生组织预认证，用于治疗资源有限国家的HIV感染患者。然而，尽管其广泛使用，但由于有效性、安全性和质量方面的临床数据稀缺，一些主要捐助机构尚未推荐使用。我们旨在评估非洲最常用的一种治疗方案，即奈韦拉平、司他夫定和拉米夫定的通用型固定剂量复方制剂的这些问题。

方法

在喀麦隆进行了一项开放标签、为期24周的多中心试验，对60名患者进行了随访。所有患者每天服用一片固定剂量复方药物，每日两次。主要结局指标是在意向性分析中，研究期末病毒载量低于每毫升400拷贝的患者比例。

研究结果

基线时，92%的患者（n = 55）患有艾滋病；CD4细胞计数中位数为每微升118个细胞（四分位距78 - 167），血浆HIV - 1 RNA中位数为每毫升104736拷贝（40804 - 243787）。治疗24周后病毒载量不可检测（<每毫升400拷贝）的患者比例为80%（95%置信区间68 - 89）。病毒载量的中位数（四分位距）变化为每毫升-3.1 log10拷贝（-2.5至-3.6），CD4细胞计数变化为每微升83个细胞（40 - 178）。存活或无新的艾滋病定义事件的概率为0.85（95%置信区间0.73 - 0.92）。疾病进展频率为每100人年32.0（95%置信区间16.6 - 61.5），严重不良反应为17.8（7.4 - 42.7），基因型耐药突变率为7.1（1.8 - 28.4）。报告的平均依从率为99%。片剂中的药物浓度中位数，奈韦拉平为预期值的96%，司他夫定为89%，拉米夫定为99%。