OBJECTIVE: The objective of this study was to systematically characterize the incidence and determinants of antiretroviral resistance in the HOMER (Highly Active Antiretroviral Therapy [HAART] Observational Medical Evaluation and Research) cohort of 1191 human immunodeficiency virus-infected, antiretroviral-naive adults initiating HAART in British Columbia, Canada. METHODS: All plasma samples with plasma virus loads (pVLs) >1000 copies/mL collected during the first 30 months of follow-up were genotyped for drug resistance. The primary outcome measure was time to the first detection of major drug-resistance mutation(s). Cox proportional hazard regression was used to identify factors significantly associated with the detection of drug-resistance mutations. RESULTS: Drug-resistance mutations were detected in 298 subjects (25%). Factors significantly associated with detection of drug-resistance mutations included high baseline pVL (multivariate hazard ratio [HR], 1.59; P<.001) and adherence (estimated using prescription-refill data and/or untimed plasma drug-concentration measurements). When compared with subjects with low (0%-<20%) prescription-refill percentages, subjects at an elevated risk of harboring drug-resistance mutations were those with relatively high but imperfect prescription-refill percentages (80%-<90%; multivariate HR, 4.15; P<.001) and those with essentially perfect (>/=95%) refill percentages but with 2 plasma drug concentrations below the steady-state trough concentration minus 1 standard deviation (multivariate HR, 4.57; P<.001). Initial use of nonnucleoside reverse-transcriptase inhibitor-based HAART was significantly associated with multiclass drug resistance (multivariate HR, 1.84; P=.001). CONCLUSION: High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.
OBJECTIVE: The objective of this study was to systematically characterize the incidence and determinants of antiretroviral resistance in the HOMER (Highly Active Antiretroviral Therapy [HAART] Observational Medical Evaluation and Research) cohort of 1191 human immunodeficiency virus-infected, antiretroviral-naive adults initiating HAART in British Columbia, Canada. METHODS: All plasma samples with plasma virus loads (pVLs) >1000 copies/mL collected during the first 30 months of follow-up were genotyped for drug resistance. The primary outcome measure was time to the first detection of major drug-resistance mutation(s). Cox proportional hazard regression was used to identify factors significantly associated with the detection of drug-resistance mutations. RESULTS: Drug-resistance mutations were detected in 298 subjects (25%). Factors significantly associated with detection of drug-resistance mutations included high baseline pVL (multivariate hazard ratio [HR], 1.59; P<.001) and adherence (estimated using prescription-refill data and/or untimed plasma drug-concentration measurements). When compared with subjects with low (0%-<20%) prescription-refill percentages, subjects at an elevated risk of harboring drug-resistance mutations were those with relatively high but imperfect prescription-refill percentages (80%-<90%; multivariate HR, 4.15; P<.001) and those with essentially perfect (>/=95%) refill percentages but with 2 plasma drug concentrations below the steady-state trough concentration minus 1 standard deviation (multivariate HR, 4.57; P<.001). Initial use of nonnucleoside reverse-transcriptase inhibitor-based HAART was significantly associated with multiclass drug resistance (multivariate HR, 1.84; P=.001). CONCLUSION: High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.
Authors: James T Pfeiffer; Manuel Napúa; Bradley H Wagenaar; Falume Chale; Roxanne Hoek; Mark Micek; João Manuel; Cathy Michel; Jessica Greenberg Cowan; James F Cowan; Sarah Gimbel; Kenneth Sherr; Stephen Gloyd; Rachel R Chapman Journal: J Acquir Immune Defic Syndr Date: 2017-11-01 Impact factor: 3.731
Authors: Susannah M Allison; Linda J Koenig; Stephanie L Marhefka; Rosalind J Carter; Elaine J Abrams; Marc Bulterys; Vicki Tepper; Paul E Palumbo; Pamela J Bachanas; John J Farley Journal: J Assoc Nurses AIDS Care Date: 2010-05-07 Impact factor: 1.354
Authors: M R Jordan; D E Bennett; M A Wainberg; D Havlir; S Hammer; C Yang; L Morris; M Peeters; A M Wensing; N Parkin; J B Nachega; A Phillips; A De Luca; E Geng; A Calmy; E Raizes; P Sandstrom; C P Archibald; J Perriëns; C M McClure; S Y Hong; J H McMahon; N Dedes; D Sutherland; S Bertagnolio Journal: Clin Infect Dis Date: 2012-05 Impact factor: 9.079
Authors: Jean B Nachega; Richard E Chaisson; Rene Goliath; Anne Efron; Mohammad A Chaudhary; Malathi Ram; Chelsea Morroni; Hennie Schoeman; Amy R Knowlton; Gary Maartens Journal: AIDS Date: 2010-06-01 Impact factor: 4.177