Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance in a Large U.S. Clinic Population. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Rhee, S., Clutter, D., Fessel, W. J., Klein, D., Slome, S., Pinsky, B. A., Marcus, J. L., Hurley, L., Silverberg, M. J., Kosakovsky Pond, S. L., Shafer, R. W. 2018


Background: There are few large studies of transmitted drug resistance (TDR) prevalence and the drug resistance mutations (DRMs) responsible for TDR in the U.S.Methods: HIV-1 RT and protease sequences were obtained from 4,253 antiretroviral therapy (ART)-naive individuals in a California clinic population from 2003-2016. Phylogenetic analyses were performed to study linkages between TDR strains and selection pressure on TDR-associated DRMs.Results: From 2003-2016, there was a significant increase in overall (odds ratio [OR]=1.05 per year; 95% CI: 1.03 - 1.08; p<0.001) and nonnucleoside RT inhibitor (NNRTI)-associated TDR (OR=1.11 per year; 95% CI: 1.08 - 1.15; p<0.001). Between 2012 and 2016, TDR rates to any drug class ranged from 15.7%-19.2%, and class-specific rates ranged from 10.0%-12.8% for NNRTIs, 4.1%-8.1% for nucleoside RT inhibitors (NRTIs), and 3.6%-5.2% for protease inhibitors. K103N/S, Y181C, Y188L, and G190A mutations accounted for 88.5% of NNRTI-associated TDR. The thymidine analog mutations, M184V/I, and the tenofovir-associated DRMs K65R and K70E/Q/G/N/T accounted for 82.9%, 7.3%, and 1.4% of NRTI-associated TDR, respectively. The proportions of individuals with low-level resistance or higher to boosted atazanavir and darunavir were 2.2% and 0.3%, respectively. 37% of TDR strains clustered with other TDR strains sharing the same DRMs.Conclusions: Although TDR has increased significantly in this large cohort, many TDR strains are unlikely to influence the activity of currently preferred first-line ART regimens. The high proportion of DRMs associated with infrequently used regimens combined with the clustering of TDR strains suggest that some TDR strains are being transmitted between ART-naive individuals.

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