Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients

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.