Landman Roland, Koulla-Shiro Sinata, Sow Papa Salif, Ngolle Maguy, Diallo Mahamadou-Baila, Guèye Ndèye Fatou Ngom, Le Moing Vincent, Eymard-Duvernay Sabrina, Benalycherif Aïda, Charpentier Charlotte, Peytavin Gilles, Delaporte Eric, Girard Pierre-Marie
Department of Infectious Diseases, Bichat Claude Bernard Hospital and Université Paris Diderot, Paris, France.
Antivir Ther. 2014;19(1):51-9. doi: 10.3851/IMP2675. Epub 2013 Aug 23.
The aim of the present study was to determine appropriate tenofovir-based regimens meriting evaluation in large-scale randomized trials among sub-Saharan African patients.
This was a randomized open-label 96-week prospective pilot study evaluating four first-line regimens: tenofovir/emtricitabine/nevirapine (group 1), tenofovir/lopinavir/ritonavir (group 2), tenofovir/emtricitabine/zidovudine (group 3) and tenofovir/emtricitabine/efavirenz (group 4) in antiretroviral-naive, HIV-1-infected patients in Senegal and Cameroon. The primary end point was defined as an HIV-1 RNA viral load <50 copies/ml (study detection limit) at week 16 in ≥50% of patients using intention-to-treat analysis.
At baseline, 119 patients included were 34% male, had a median plasma viral load of 5.4 log10 copies/ml and median CD4(+) T-cell count of 200 cells/mm(3) (range 53-358). The primary end point was achieved for groups 1, 3 and 4 (58% [n=31], 62% [n=29] and 53% [n=30], respectively), but not for group 2 (38% [n=29]). At week 96, undetectable HIV-1 RNA had been achieved in 74% of patients in group 1, 38% in group 2, 72% in group 3 and 73% in group 4. Patients with detectable HIV-1 RNA at week 16 were more likely to have baseline HIV-1 RNA≥100,000 copies/ml (adjusted OR 5.56, 95% CI 1.72, 16.67). HIV mutations associated with protease inhibitor resistance emerged in three patients, all of whom were in group 2. Anaemia occurred in two group 3 patients and was the only serious treatment-related adverse event.
Three efficient and safe tenofovir-based triple regimens were identified; the two-drug regimen (tenofovir/lopinavir/ritonavir) did not achieve the protocol-defined virological threshold of efficacy.
本研究的目的是确定在撒哈拉以南非洲患者中值得在大规模随机试验中进行评估的基于替诺福韦的合适治疗方案。
这是一项随机开放标签的96周前瞻性试验研究，在塞内加尔和喀麦隆未接受过抗逆转录病毒治疗的HIV-1感染患者中评估四种一线治疗方案：替诺福韦/恩曲他滨/奈韦拉平（第1组）、替诺福韦/洛匹那韦/利托那韦（第2组）、替诺福韦/恩曲他滨/齐多夫定（第3组）和替诺福韦/恩曲他滨/依非韦伦（第4组）。主要终点定义为在第16周时，采用意向性分析，≥50%的患者的HIV-1 RNA病毒载量<50拷贝/ml（研究检测限）。
基线时，纳入的119例患者中34%为男性，血浆病毒载量中位数为5.4 log10拷贝/ml，CD4(+) T细胞计数中位数为200个细胞/mm(3)（范围53 - 358）。第1、3和4组达到了主要终点（分别为58% [n = 31]、62% [n = 29]和53% [n = 30]），但第2组未达到（38% [n = 29]）。在第96周时，第1组74%的患者、第2组38%的患者、第3组72%的患者和第4组73%的患者实现了HIV-1 RNA检测不到。在第16周时HIV-1 RNA可检测到的患者更有可能基线HIV-1 RNA≥100,000拷贝/ml（调整后的比值比5.56，95%置信区间1.72，16.67）。与蛋白酶抑制剂耐药相关的HIV突变出现在3例患者中，所有这些患者均在第2组。第3组有2例患者发生贫血，这是唯一与治疗相关的严重不良事件。
确定了三种有效且安全的基于替诺福韦的三联治疗方案；两药方案（替诺福韦/洛匹那韦/利托那韦）未达到方案定义的病毒学疗效阈值。
