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Limited Evolution of HIV Antiretroviral Drug Resistance-Associated Mutations During the Performance of Drug Resistance Testing

Birch Chris; Middleton, Tracey; Hales, Gillian; Cooper, David; Law, Matthew; Crowe, Suzanne; Hoy, Jennifer; Emery, Sean
JAIDS Journal of Acquired Immune Deficiency Syndromes: January 2003

We investigated the evolution of HIV reverse transcriptase (RT)- and protease-associated antiretroviral (ARV) drug resistance mutations during the time taken to perform genotypic drug resistance testing. Thirty treatment-experienced patients who were adherent to therapy and who underwent genotypic drug resistance testing provided blood samples at randomization and when reviewing the test results (baseline). Patients remained on their existing therapy between randomization and baseline. The predominant HIV strains in 10 patients (33%) either lost and/or gained primary RT inhibitor (RTI)- or protease inhibitor (PI)-associated resistance mutations during the testing period. Of the 9 patients with RT mutations, 2 lost, 5 gained, and 2 both lost and gained RTI resistance mutations. One patient gained a significant PI- associated resistance mutation on an existing PI-resistant background. The evolution that occurred in the RT may have altered the effectiveness of subsequent ARV therapy in some patients. Neither viral load at randomization, ARV drug class used at randomization, time between collection of blood samples, duration of current therapy, nor number of ARV drugs used influenced gain or loss of resistance mutations. There was a significant association between duration of previous ARV therapy and gain of RTIassociated resistance mutations (p = .02), however. In general, our results suggest that patients should continue current therapy until test results are available. A few patients would be expected to gain ARV drug-associated resistance mutations during this time, however.

The NCHECR is funded by the Commonwealth Department of Health and Aged Care. The following companies provided financial support: Diagnostic Technology, Perkin Elmer Biosystems, Abbott Australasia, Boehringer Ingelheim, Bristol-Myers Squibb, Glaxo- SmithKline, Merck Sharpe and Dohme, and Roche Pharmaceuticals.

Address correspondence and reprint requests to Chris Birch, Victorian Infectious Diseases Reference Laboratory, 10 Wreckyn Street, North Melbourne 3051, Victoria, Australia; e-mail:

Manuscript received June 25, 2002; accepted October 21, 2002.

© 2003 Lippincott Williams & Wilkins, Inc.