Geographic and temporal trends of transmitted hiv-1 drug resistance among antiretroviral-naïve subjects screening for two clinical trials in North America and Western Europe

Abstract

Purpose: To determine the prevalence of transmitted drug resistance (TDR) in antiretroviral (ARV)-naïve HIV-1-infected subjects who were screened for two clinical trials by geographic region and time. Methods: Studies M03-613 and M05-730 screened ARV-naïve subjects in 2004 and 2005-2006, respectively. Screening drug resistance genotype assays were performed using population sequencing, and prevalence of drug resistance mutations (DRMs) was assessed at 39 amino acid positions in HIV-1 protease and reverse transcriptase (RT) and compared between geographic regions and calendar years. Results: In 913 subjects, the prevalence of DRMs was higher in North America than in Western Europe, including any DRM (13.6% vs. 6.8%, p < .001), non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs (7.3% vs. 3.2%, p = .006), protease inhibitor (PI) DRMs (3.6% vs. 0.8%, p = .004), and nucleoside reverse transcriptase inhibitor (NRTI) DRMs (6.1% vs. 3.8%, p = ns). The prevalence of TDR to NNRTIs was higher compared to PIs within each region (p = .031 for North America, and p = .011 for Western Europe). Logistic regression analysis suggested a higher prevalence of DRMs in 2005-2006 compared to 2004 for NNRTIs (p = .03) and, to a lesser extent, for PIs (p = .07). Conclusion: TDR to NNRTIs was more frequent than to PIs in both geographic regions, increased over time, and was highest in North America. © 2009 Thomas Land Publishers, Inc.