HIV genotypes of treatment-naïve patients receiving adefovir dipivoxil in a highly active antiretroviral therapy regimen.
Originally Published on July 20, 1999
Margot NA, Anton KE, Miller MD.
6th Conference on Retroviruses and Opportunistic Infections. 31 Jan-4 Feb, 1999, Chicago, IL. Abstract 112.
ABSTRACT:
GS-96-411 is a phase III clinical trial assessing the safety and efficacy of adefovir dipivoxil (ADV) as part of combination antiretroviral therapy in treatment-naïve patients. All patients received indinavir (IDV) and were randomized to additionally receive ADV+AZT+3TC, ADV+AZT, ADV+3TC, ADV+d4T or, as a control, AZT+3TC. In this interim analysis, 98 patients have completed 20 weeks of therapy and similar proportions of patients on treatment in all arms (79-83%) achieved plasma HIV RNA levels of <400 copies/ml. A total of 18 patients (18%) had detectable (>400 copies/ml) levels of HIV RNA at multiple time points, including week 20, and were equivalently distributed across all 5 arms. The HIV RT and protease genes from both baseline and week 20 plasma samples were sequenced from these 18 patients. One patient developed the IDV-associated V82A protease resistance mutation. Two patients, one from the IDV/ADV/3TC arm and one from the control IDV/AZT/3TC arm, developed the 3TC-associated M184V RT mutation. Interestingly, one patient entered the study with an M41L RT mutation and an unusual RT mutation, T215D, possibly due to the transmission of AZT-resistant HIV. This patient responded to IDV/ADV/d4T therapy, and a corresponding recombinant virus showed wild-type drug susceptibilities to ADV, d4T, and AZT. Thus, of the 18% of treatment-naïve patients in this study who had detectable HIV RNA at week 20, the majority (15 of 18) showed no genetic basis for their HIV detectability, suggesting possible non-adherence and/or inadequate drug levels in these patients. Thus, at 20 weeks, patients in all ADV-containing treatment arms responded similarly to control arm patients in terms of HIV RNA reductions and HIV genotypes in detectable patients.
