Squires Kathleen, Pozniak Anton L, Pierone Gerald, Steinhart Corklin R, Berger Daniel, Bellos Nicholaos C, Becker Stephen L, Wulfsohn Michael, Miller Michael D, Toole John J, Coakley Dion F, Cheng Andrew
Keck School of Medicine, University of Southern California, Los Angeles, USA.
Ann Intern Med. 2003 Sep 2;139(5 Pt 1):313-20. doi: 10.7326/0003-4819-139-5_part_1-200309020-00006.
Resistance to antiretroviral agents remains a leading cause of treatment failure for patients infected with HIV-1.
To describe the efficacy and safety of tenofovir disoproxil fumarate (tenofovir DF) compared with placebo in patients with detectable viral replication despite current antiretroviral therapy.
Randomized, double-blind, placebo-controlled study through 24 weeks. After 24 weeks, all patients received open-label tenofovir DF for the remainder of the 48-week study.
75 North American, European, and Australian HIV clinics.
552 HIV-1-infected adults who were receiving antiretroviral therapy and had stable HIV-1 RNA levels ranging from 400 to 10,000 copies/mL.
Change in HIV-1 RNA level (time-weighted average from baseline through week 24); proportion of patients with grade 3 or 4 laboratory abnormalities and adverse events; and genotypic HIV-1 resistance testing in a separate substudy at baseline, week 24, and week 48.
A statistically significant decrease in HIV-1 RNA level through week 24 (the primary end point) was observed in the tenofovir DF group versus the placebo group (-0.61 log10 copies/mL vs. -0.03 log10 copies/mL, respectively [P < 0.001]; difference, -0.58 log10 copies/mL [95% CI, -0.68 to -0.49 log10 copies/mL]). In a virologic substudy, 94% of 253 patients had plasma isolates expressing reverse transcriptase mutations associated with nucleoside resistance mutations at baseline. Through week 24, the incidence of clinical adverse events was similar between patients receiving placebo and those receiving tenofovir DF (14% vs. 13%). No evidence of tenofovir DF-related toxicity was seen through week 48.
In treatment-experienced patients with suboptimal viral suppression, tenofovir DF significantly reduced HIV-1 RNA level and had a safety profile similar to that of placebo.
对抗逆转录病毒药物的耐药性仍然是人类免疫缺陷病毒1型（HIV-1）感染患者治疗失败的主要原因。
描述富马酸替诺福韦二吡呋酯（替诺福韦DF）与安慰剂相比，在当前接受抗逆转录病毒治疗但病毒仍可检测到复制的患者中的疗效和安全性。
为期24周的随机、双盲、安慰剂对照研究。24周后，在为期48周的研究剩余时间里，所有患者接受开放标签的替诺福韦DF治疗。
75家北美、欧洲和澳大利亚的HIV诊所。
552名接受抗逆转录病毒治疗且HIV-1 RNA水平稳定在400至10,000拷贝/毫升的HIV-1感染成人。
HIV-1 RNA水平的变化（从基线到第24周的时间加权平均值）；3级或4级实验室异常和不良事件的患者比例；以及在基线、第24周和第48周的一项单独子研究中进行的HIV-1基因型耐药性检测。
与安慰剂组相比，替诺福韦DF组在第24周时（主要终点）HIV-1 RNA水平有统计学显著下降（分别为-0.61 log10拷贝/毫升和-0.03 log10拷贝/毫升[P < 0.001]；差异为-0.58 log10拷贝/毫升[95% CI，-0.68至-0.49 log10拷贝/毫升]）。在一项病毒学子研究中，253名患者中有94%在基线时血浆分离株表达与核苷耐药突变相关的逆转录酶突变。到第24周时，接受安慰剂和接受替诺福韦DF治疗的患者临床不良事件发生率相似（分别为14%和13%）。在第48周时未发现替诺福韦DF相关毒性的证据。
在病毒抑制效果欠佳的经治患者中，替诺福韦DF显著降低了HIV-1 RNA水平，且安全性与安慰剂相似。
