Genotypic and Phenotypic Predictors of the Magnitude of Response to Tenofovir in Treatment-experienced HIV Patients

Results from 2 placebo-controlled intensification trials of tenofovir disoproxil fumarate/ TDF (Viread) in treatment-experienced HIV-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 >or=3 TAMs (n=147).

Response to tenofovir DF was reduced among patients with HIV-1 with >or=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.

Gilead Sciences, Foster City, California.

04/09/04

Reference
M D Miller and others. Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. Journal of Infectious Diseases 189(5): 837-846. March 1, 2004.