Martínez Esteban, Arnaiz Juan A, Podzamczer Daniel, Dalmau David, Ribera Esteban, Domingo Pere, Knobel Hernando, Riera Melcior, Pedrol Enric, Force Lluis, Llibre Josep M, Segura Ferran, Richart Cristóbal, Cortés Cristina, Javaloyas Manuel, Aranda Miquel, Cruceta Ana, de Lazzari Elisa, Gatell José M
Infectious Diseases Unit, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain.
N Engl J Med. 2003 Sep 11;349(11):1036-46. doi: 10.1056/NEJMoa021589.
We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved.
We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter.
At 12 months, the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups.
When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.
我们评估了在已实现病毒学抑制的1型人类免疫缺陷病毒（HIV-1）感染者中，用奈韦拉平、依非韦伦或阿巴卡韦替代蛋白酶抑制剂的策略。
我们将460名正在服用两种核苷类逆转录酶抑制剂和至少一种蛋白酶抑制剂且血浆HIV-1 RNA水平在至少过去六个月中低于每毫升200拷贝的成年人随机分配，使其从蛋白酶抑制剂转换为奈韦拉平（155例患者）、依非韦伦（156例）或阿巴卡韦（149例）。主要终点是死亡、进展为获得性免疫缺陷综合征或HIV-1 RNA水平升高至每毫升200拷贝或更多。
在12个月时，根据意向性分析，奈韦拉平组达到终点的可能性的Kaplan-Meier估计值为10%，依非韦伦组为6%，阿巴卡韦组为13%（P = 0.10）。在接受研究药物治疗期间发生病毒学失败的29例患者中，有21例（72%）的HIV-1 RNA可被扩增，并且在这21例患者中，除1例之外，均检测到对研究药物以及对失败治疗方案中至少一种核苷类逆转录酶抑制剂的耐药突变。在接受研究药物治疗期间发生病毒学失败的29例患者中，有23例之前接受过核苷类逆转录酶抑制剂的次优治疗。因不良事件而停用研究药物的阿巴卡韦组患者（6%）少于奈韦拉平组（17%）或依非韦伦组（17%）（P = 0.01）。阿巴卡韦组中需要进行治疗干预的空腹血脂水平患者比例显著下降，但三组中临床脂肪营养不良的患病率没有显著变化。
在病毒学得到抑制的患者中，当治疗从蛋白酶抑制剂转换为奈韦拉平、依非韦伦或阿巴卡韦时，接受阿巴卡韦治疗的患者中病毒学失败率有升高趋势。
