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Risk of extensive virological failure to the three original antiretroviral drug classes over long-term follow-up from the start of therapy in patients with HIV infection: an observational cohort study.

Phillips AN, Leen C, Wilson A, Anderson J, Dunn D, Schwenk A, Orkin C, Hill T, Fisher M, Walsh J, Pillay D, Bansi L, Gazzard B, Easterbrook P, Gilson R, Johnson M, Sabin CA,

Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK. a.phillips@pcps.ucl.ac.uk

BACKGROUND: The long-term durability of viral-load suppression provided by the three original antiretroviral drugs is not well characterised. We estimated the proportion of patients who had extensive triple-class failure during long-term follow-up and examined characteristics associated with an increased rate of failure. METHODS: 7916 patients who started antiretroviral therapy with three or more drugs were followed up from the time that therapy started until the last viral-load measure. Extensive triple-class virological failure was defined by failure of three subclasses of nucleoside reverse transcriptase inhibitors, a non-nucleoside reverse transcriptase inhibitor, and a ritonavir-boosted protease inhibitor. FINDINGS: 167 patients developed extensive triple-class failure during 27 441 person-years of follow-up. The Kaplan-Meier estimate for the cumulative risk of extensive triple-class failure was 9.2% by 10 years (95% CI 5.0-13.4). There was evidence that this rate has decreased over time (adjusted hazard ratio 0.86 [0.77-0.96] per year more recent; p=0.006). Of the 167 patients with extensive triple-class failure, 101 (60%) subsequently had at least one viral load less than 50 copies per mL. The risk of death by 5 years from the time of extensive triple-class failure was 10.6% (2.4-18.8, nine deaths). INTERPRETATION: We have shown that extensive virological failure of the three main classes of drugs occurs slowly in routine clinical practice. This finding has implications for the planning of treatment programmes in developing countries, where additional drugs outside these classes are unlikely to be available for some time.

Published 10 December 2007 in Lancet, 370(9603): 1923-8.
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