Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients
Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients
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DOI：
10.1086/381784
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发表时间：
2004-03-01
影响因子：
6.4
通讯作者：
Wulfsohn, M
中科院分区：
文献类型：
--
作者：
Miller, MD;Margot, N;Wulfsohn, M
对富马酸替诺福韦酯（DF）在经治疗的人类免疫缺陷1型（HIV-1）感染患者（n = 332）中进行的2项安慰剂对照强化试验的结果进行整合，以确定基线耐药对HIV-1 RNA应答的影响。在这些试验中，HIV-1耐药突变的患病率很高，94%的患者有核苷相关突变，71%的患者有胸苷类似物相关突变（TAM）。与安慰剂相比，在无TAM的患者（n = 97）或有1 - 2个TAM（n = 88）或≥3个TAM（n = 147）的患者中观察到替诺福韦DF治疗相关的HIV-1 RNA统计学显著降低（P <0.001）。在携带≥3个TAM（包括M41 L或L210 W突变）的HIV-1患者（n = 86）或既存K65 R突变的患者（n = 6）中，替诺福韦DF的应答降低。当存在M184 V突变时，观察到治疗应答略微增加。对于替诺福韦DF开始降低应答和强烈降低应答，表型临界值分别确定为1.4倍和4倍。这些对照临床试验的结果为有治疗经验的患者使用替诺福韦DF提供了指导。
Results from 2 placebo-controlled intensification trials of tenofovir disoproxil fumarate (DF) in treatment-experienced human immunodeficiency type 1 (HIV-1)- infected patients (n = 332) were integrated to determine the effects of resistance at baseline on HIV-1 RNA response. In these trials, there was a high prevalence of HIV-1 resistance mutations, with 94% of patients having nucleoside-associated mutations and 71% having thymidine analogue - associated mutations (TAMs). Statistically significant HIV-1 RNA reductions associated with tenofovir DF treatment, relative to placebo (P < .001), were observed for patients without TAMs (n = 97) or for patients with 1 - 2 (n = 88) or ≥3 TAMs (n = 147). Response to tenofovir DF was reduced among patients with HIV-1 with ≥3 TAMs inclusive of either the M41L or L210W mutation (n = 86) or patients who had a preexisting K65R mutation (n = 6). Slightly increased treatment responses were observed when the M184V mutation was present. Phenotypic cutoffs were established at 1.4-fold and 4-fold, respectively, for the beginning of reduced response to tenofovir DF and for a strongly reduced response. The results from these controlled clinical trials provide guidance for the use of tenofovir DF for treatment-experienced patients.