Miro Jose M, Manzardo Christian, Ferrer Elena, Loncà Montserrat, Guardo Alberto C, Podzamczer Daniel, Domingo Pere, Curran Adrian, Clotet Bonaventura, Cruceta Anna, Lozano Francisco, Pérez Iñaki, Plana Montserrat, Gatell Jose M
*Group of Immune receptors of the Innate and Adaptive System, IDIBAPS, Barcelona, Spain; †Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; ‡Immunology Department, Hospital Clínic de Barcelona, Barcelona Spain, University of Barcelona, Barcelona, Spain; §Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; ‖Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; and ¶Hospital Germans Trias i Pujols, Irsicaixa, Universitat Autònoma de Barcelona, UVic, Badalona, Spain.
J Acquir Immune Defic Syndr. 2015 Jun 1;69(2):206-15. doi: 10.1097/QAI.0000000000000567.
Few randomized clinical trials have investigated antiretroviral regimens in very advanced HIV-1-infected patients. The objective was to study the immune reconstitution in very immunosuppressed antiretroviral-naive, HIV-1-infected individuals by comparing an efavirenz-based regimen with 2 ritonavir-boosted protease inhibitor regimens.
Randomized, controlled, open-label, multicenter clinical trial. Eighty-nine HIV-1-infected antiretroviral-naive patients with <100 CD4 cells per cubic millimeter were randomly assigned in a 1:1:1 ratio to efavirenz (n = 29), atazanavir/ritonavir (n = 30), or lopinavir/ritonavir (n = 30) combined with tenofovir plus emtricitabine. The primary outcome was median increase in CD4 cell count at week 48. Secondary end points were the proportion of patients with HIV-1 RNA <50 copies per milliliter, adverse events, disease progression, and death.
In the on-treatment analysis, the median (interquartile range) increase in the CD4 count after 48 weeks was +193 (129-349) cells per microliter in the efavirenz arm, +197 (146-238) cells per microliter in the ritonavir-boosted atazanavir arm, and +205 (178-327) cells per microliter in the ritonavir-boosted lopinavir arm (P = 0.73). The percentage of patients achieving viral suppression was similar in all 3 treatment arms at 48 weeks {efavirenz, 85.71% [95% confidence interval (CI): 68.5 to 94.3]; atazanavir, 80% [95% CI: 62.7 to 90.5]; and lopinavir, 82.8% [95% CI: 65.5 to 92.4]; P = 0.88}. Bacterial translocation, inflammation, immune activation, and apoptotic markers, but not D-dimer, declined significantly and similarly in the 3 treatment arms. Adverse events had a similar incidence in all 3 antiretroviral regimens. No patients died.
The immune reconstitution induced by an efavirenz-based regimen in very advanced HIV-1-infected patients was similar to that induced by a ritonavir-boosted protease inhibitor-based regimen (ClinicalTrials.gov registration number: NCT00532168).
很少有随机临床试验研究在HIV-1感染非常严重的患者中使用抗逆转录病毒治疗方案。目的是通过比较基于依非韦伦的治疗方案与两种利托那韦增强的蛋白酶抑制剂治疗方案，研究在未接受过抗逆转录病毒治疗、免疫抑制非常严重的HIV-1感染个体中的免疫重建情况。
随机、对照、开放标签、多中心临床试验。89例未接受过抗逆转录病毒治疗、HIV-1感染且每立方毫米CD4细胞数少于100个的患者，按1:1:1的比例随机分配至依非韦伦组（n = 29）、阿扎那韦/利托那韦组（n = 30）或洛匹那韦/利托那韦组（n = 30），同时联合替诺福韦加恩曲他滨。主要结局是第48周时CD4细胞计数的中位数增加量。次要终点包括HIV-1 RNA低于每毫升50拷贝的患者比例、不良事件、疾病进展和死亡情况。
在治疗期分析中，依非韦伦组48周后CD4计数的中位数（四分位间距）增加量为每微升+193（129 - 349）个细胞，利托那韦增强的阿扎那韦组为每微升+197（146 - 238）个细胞，利托那韦增强的洛匹那韦组为每微升+205（178 - 327）个细胞（P = 0.73）。在第48周时，所有3个治疗组实现病毒抑制的患者百分比相似{依非韦伦组为85.71%[95%置信区间（CI）：68.5至94.3]；阿扎那韦组为80%[95%CI：62.7至90.5]；洛匹那韦组为82.8%[95%CI：65.5至92.4]；P = 0.88}。3个治疗组中细菌易位、炎症、免疫激活和凋亡标志物（但不包括D-二聚体）均显著且相似地下降。所有3种抗逆转录病毒治疗方案的不良事件发生率相似。无患者死亡。
在HIV-1感染非常严重的患者中，基于依非韦伦的治疗方案诱导的免疫重建与基于利托那韦增强的蛋白酶抑制剂的治疗方案相似（ClinicalTrials.gov注册号：NCT00532168）。
