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 treatmentexperienced human immunodeficiency type 1 (HIV-1)‐infected patients ( ) were integrated to determine n p 332 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 ( ), were observed for patients without TAMs ( P ! .001 n p ) or for patients with 1‐2 ( ) or 3 TAMs ( ). Response to tenofovir DF was reduced among 97 n p 88 n p 147 patients with HIV-1 with 3 TAMs inclusive of either the M41L or L210W mutation ( ) or patients n p 86 who had a preexisting K65R mutation ( ). Slightly increased treatment responses were observed when n p 6 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.