Response to therapy with adefovir dipivoxil is durable for 48 weeks and correlates with baseline HIV genotype and in vitro susceptibility to adefovir.
Originally Published on July 20, 1999
Miller MD, Anton KE, Margot NA, Lamy PD, Mulato AS.
6th Conference on Retroviruses and Opportunistic Infections. 31 Jan-4 Feb, 1999, Chicago, IL. Abstract 137.
ABSTRACT:
GS-96-408 was a phase III clinical trial assessing adefovir dipivoxil (ADV) compared to placebo for the treatment of HIV. 142 patients were prospectively selected for a virology substudy. At week 24, the ADV-treated patients in the substudy showed a statistically significant median 0.53 log10 decrease in plasma HIV RNA versus an 0.01 log10 increase for placebo patients (p < 0.0001). Patients were grouped according to their baseline RT genotypes for AZT and 3TC resistance mutations. 53%, 8% and 15% had high-level, low-level or no AZT resistance mutations, respectively, along with the M184V 3TC resistance mutation, and showed statistically significant median decreases in HIV RNA of 0.51, 0.75 and 0.94 log10 at week 24, respectively. 14%, 4% and 6% of patients had high-level, low-level or no AZT resistance mutations, respectively, without the M184V mutation, and showed median decreases in HIV RNA of 0.05, 0.65 and 0.65 log10, respectively. Thus, 86% of patients were in the 5 responsive groups, including the largest group of patients (53%) with both high-level AZT and 3TC resistance mutations. These responses were durable in patients who continued ADV therapy for 32-48 weeks. Phenotypic analyses were performed with baseline RT recombinant viruses from 18 patients representing the 6 genetic groups. Recombinant viruses from patients in the 5 responsive groups showed IC50 values for adefovir that were wild-type or within 3-fold of wild-type; whereas viruses from the non-responsive group were >5-fold above wild-type. From these retrospective analyses, these data suggest that both genotypic and phenotypic testing can be used to predict response to adefovir dipivoxil therapy in patients on stable antiretroviral therapy. Furthermore, such responses can be durable for 48 weeks.
