Lazzarin Adriano, Clotet Bonaventura, Cooper David, Reynes Jacques, Arastéh Keikawus, Nelson Mark, Katlama Christine, Stellbrink Hans-Jürgen, Delfraissy Jean-François, Lange Joep, Huson Les, DeMasi Ralph, Wat Cynthia, Delehanty John, Drobnes Claude, Salgo Miklos
Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Vita-Salute University, Milan, Italy.
N Engl J Med. 2003 May 29;348(22):2186-95. doi: 10.1056/NEJMoa035211.
The T-20 vs. Optimized Regimen Only Study 2 (TORO 2) compared the efficacy and safety of 24 weeks of treatment with the fusion inhibitor enfuvirtide in combination with an optimized background antiretroviral regimen with the efficacy and safety of the optimized background regimen alone.
The patients had previous treatment with each of the three classes of antiretroviral drugs, documented resistance to each class, or both and a plasma level of human immunodeficiency virus type 1 (HIV-1) RNA of at least 5000 copies per milliliter. They were randomly assigned in a 2:1 ratio to receive either enfuvirtide (90 mg twice daily) plus a background regimen optimized with the aid of resistance testing (enfuvirtide group) or the background regimen alone (control group).
Of the 512 patients who underwent randomization, 335 in the enfuvirtide group and 169 in the control group received at least one dose of study medication and had at least one follow-up measurement of plasma HIV-1 RNA. The median base-line plasma HIV-1 RNA level was 5.1 log10 copies per milliliter in both groups. The median CD4+ cell count was 98.0 cells per cubic millimeter in the enfuvirtide group and 101.5 cells per cubic millimeter in the control group. Patients had a median of seven years of previous treatment and had received a median of 12 antiretroviral drugs. The background regimen comprised a mean of four antiretroviral drugs in both groups. At 24 weeks, the least-squares mean change from base line in the plasma viral load (intention-to-treat, last observation carried forward) was a decrease of 1.429 log10 copies per milliliter in the enfuvirtide group and a decrease of 0.648 log10 copies per milliliter in the control group, a difference of 0.781 log10 copies per milliliter (P<0.001). The mean increase in the CD4+ cell count was greater in the enfuvirtide group (65.5 cells per cubic millimeter) than in the control group (38.0 cells per cubic millimeter, P=0.02).
The addition of enfuvirtide to an optimized background regimen provided significant viral suppression and immunologic benefit over a 24-week period in HIV-1-infected patients who had previously received multiple antiretroviral drugs.
T-20与优化方案单用研究2（TORO 2）比较了融合抑制剂恩夫韦肽联合优化背景抗逆转录病毒方案治疗24周的疗效和安全性与单用优化背景方案的疗效和安全性。
患者此前接受过三类抗逆转录病毒药物中的每一类治疗，有对每一类药物的耐药记录，或两者皆有，且血浆1型人类免疫缺陷病毒（HIV-1）RNA水平至少为每毫升5000拷贝。他们按2:1的比例随机分组，分别接受恩夫韦肽（每日两次，每次90毫克）加借助耐药性检测优化的背景方案（恩夫韦肽组）或单用背景方案（对照组）。
在512例接受随机分组的患者中，恩夫韦肽组335例和对照组169例接受了至少一剂研究用药，且至少有一次血浆HIV-1 RNA的随访测量。两组的基线血浆HIV-1 RNA水平中位数均为每毫升5.1 log10拷贝。恩夫韦肽组CD4+细胞计数中位数为每立方毫米98.0个细胞，对照组为每立方毫米101.5个细胞。患者此前治疗的中位数为7年，接受抗逆转录病毒药物的中位数为12种。两组的背景方案平均均包含4种抗逆转录病毒药物。在24周时，血浆病毒载量自基线的最小二乘均值变化（意向性分析，末次观察结转）在恩夫韦肽组为每毫升下降1.429 log10拷贝，在对照组为每毫升下降0.648 log10拷贝，差值为每毫升0.781 log10拷贝（P<0.001）。恩夫韦肽组CD4+细胞计数的平均增加幅度（每立方毫米65.5个细胞）大于对照组（每立方毫米38.0个细胞，P=0.02）。
对于此前接受过多种抗逆转录病毒药物治疗的HIV-1感染患者，在优化背景方案中加用恩夫韦肽在24周期间可提供显著的病毒抑制和免疫益处。
