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1 February 2005

Volume 191, Number 3
The Journal of Infectious Diseases 2005;191:339–347
© 2004 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19103-0004$15.00
DOI: 10.1086/427192
MAJOR ARTICLE

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

P. Richard Harrigan,1,2

Robert S. Hogg,1,2

Winnie W. Y. Dong,1

Benita Yip,1

Brian Wynhoven,1

Justin Woodward,1

Chanson J. Brumme,1

Zabrina L. Brumme,1,2

Theresa Mo,1

Chris S. Alexander,1 and

Julio S. G. Montaner1,2

1British Columbia Centre for Excellence in HIV/AIDS, and 2Department of Medicine, University of British Columbia, Vancouver, Canada

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; ) 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; ) 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; ). Initial use of nonnucleoside reverse‐transcriptase inhibitor–based HAART was significantly associated with multiclass drug resistance (multivariate HR, 1.84; ).

Conclusion.High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.

Received 3 June 2004; accepted 16 August 2004; electronically published 22 December 2004.

Reprints or correspondence: Dr. Richard Harrigan, 613‐1081 Burrard St., Vancouver, BC, Canada, V6Z 1Y6 ().

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  • Presented in part: 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, 13–16 July 2003 (abstract 829); 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, 8–11 February 2004 (abstract 689).

    Financial support: Canadian Institute for Health Research (a doctoral research award to Z.L.B. and an Operating Grant); Michael Smith Foundation for Health Research (a Senior Scholar award to R.S.H. and a doctoral research award to Z.L.B.).

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