Evolution of genotypic resistance algorithms and their impact on the interpretation of clinical trials: An OPTIMA trial substudy

Abstract

Purpose: The outdated rules of older HIV genotypic resistance algorithms can affect virologic responses. This study was designed to determine how often these incorrect resistance interpretations affect analyses of long-term clinical trials, antiretroviral (ARV) choices, and HIV disease progression rates. Method: Baseline VIRCO virtual phenotypes (WP) from patients screened in 2001-2002 for OPTIMA were compared to 2005 Stanford HIV resistance database algorithm (HIVDB-10/05, version 4.1.4) interpretations of the HIV-1 pol sequences. Drugs were called discordant if resistant by one algorithm and sensitive by the other. Results: Of 2,341 drug comparisons, 501 (21.4%) were discordant, affecting 140 (86.4%) of 162 screened patients. NRTI/NtRTIs were more discordant than NNRTIs and PIs (38.6% vs. 4.3% vs. 12.8%; p