Details

Autor(en) / Beteiligte

• Harrigan, P. Richard
• Hogg, Robert S.
• Dong, Winnie W. Y.
• Yip, Benita
• Wynhoven, Brian
• Woodward, Justin
• Brumme, Chanson J.
• Brumme, Zabrina L.
• Mo, Theresa
• Alexander, Chris S.
• Montaner, Julio S. G.

Titel

Predictors of HIV Drug-Resistance Mutations in a Large Antiretroviral-Naive Cohort Initiating Triple Antiretroviral Therapy

Ist Teil von

• The Journal of infectious diseases, 2005-02, Vol.191 (3), p.339-347

Ort / Verlag

Chicago, IL: The University of Chicago Press

Erscheinungsjahr

2005

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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 prescriptionrefill 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.