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Evolution of antiretroviral resistance in Ugandan patients on first-line HAART with persistent virologic failure
Presented by Steven Reynolds, United States.
Reynolds S.1, Dybul M.2, Daucher M.3, Kabuye G.4, Harvey R.3, Kityo C.4, Dewar R.3, Quinn T.3, Mugyenyi P.4
1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Washington, United States, 2US Department of State, Office of The Global AIDS Coordinator, Washington, United States, 3National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States, 4Joint Clinical Research Center, Kampala, Uganda
Objectives: To evaluate the evolution over time of genotypic antiretroviral resistance patterns among patients receiving first-line NRTI containing HAART who had evidence of persistence virologic failure.
Methods: A sub analysis of 12 participants enrolled in a randomized, controlled trial of short cycle treatment interruption who developed virologic failure (VL>400 copies/ml on at least 2 f/u visits) and remained on first-line NRTI containing HAART. Viral load and CD4 monitoring were performed every 6 weeks during follow-up. Genotypic resistance was measured using the Trugene assay at the first available and last failure visit with VL>400 copies/ml (baseline genotype available on 11/12 participants). All participants were on continuous treatment during the exposure time for this analysis.
Results: Majority of participants (11/12) were receiving 2NRTI/NNRTI combination HAART (1 participant on 2NRTI/PI). Median failure time was 46.5 weeks (range 18-69 weeks). Median VL during failure time was 31 461 (429-331789), median CD4 change was +10 cells/ul (-93 to +182). The majority (10/12) of participants reported >95% adherence by self-report and all participants remained on first line therapy throughout the period of analysis. All participants with baseline genotype on an NNRTI regimen had a K103 mutation detectable at the first failure visit (n=10). Seventy three percent of participants on 3TC containing HAART (8/11) had an M184V mutation at their first failure visit with all developing this resistance by their last failure visit. None of the participants developed any genotypic resistance to AZT/d4t during follow-up (no TAMS or Q151M complex).
Conclusions: Despite prolonged virologic failure in the setting of first line HAART, no TAMS developed in this group of participants. These findings confirm earlier data from non-RLS which suggest that AZT/d4t resistance develops slowly and these compounds may be effective in second line regimens as per the current Ugandan Ministry of Health guidelines.
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