Title: No response to first-line tenofovir + lamivudine + efavirenz despite optimization according to baseline resistance testing: impact of resistant minority variants on efficacy of low genetic barrier drugs
Authors: Van Laethem, Kristel ×
De Munter, Paul
Schrooten, Yoeri
Verbesselt, Rene
Van Ranst, Marc
Van Wijngaerden, Eric
Vandamme, Anne-Mieke #
Issue Date: May-2007
Publisher: Elsevier Science
Series Title: Journal of Clinical Virology vol:39 issue:1 pages:43-47
Conference: European HIV Drug Resistance Workshop: From Basic Science to Clinical Implications edition:5 location:Cascais date:28-30 March 2007
Abstract: BACKGROUND: Resistance testing has been implemented into clinical guidelines as it has shown some beneficial effect on subsequent therapy response. CASE REPORT: Routine population-based genotypic resistance testing for a newly diagnosed HIV-1 patient revealed the presence of resistance mutations M41L, V179D and T215E within reverse transcriptase and no mutations within protease. Four weeks after initiation of the combination tenofovir+lamivudine+efavirenz, no response was observed despite good adherence to therapy and efavirenz drug levels in the therapeutic range. Retrospective single genome sequencing of the baseline sample revealed the presence of minority viral variants with additional mutations: a mutation conferring resistance to lamivudine (M184IV), a thymidine associated mutation (K219R) and mutations possibly associated with non-nucleoside reverse transcriptase resistance (F227S, M230IV). CONCLUSIONS: This case illustrates that undetected drug-resistant minority variants can reduce the efficacy of a normally very potent first-line regimen tenofovir+lamivudine+efavirenz. The presence of drug-resistance mutations at diagnosis should be considered as a warning sign against the use of low genetic barrier drugs in first-line regimens, even when these drugs are considered to be active according to routine resistance testing.
ISSN: 1386-6532
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical and Epidemiological Virology (Rega Institute)
Laboratory for Clinical Infectious and Inflammatory Disorders
× corresponding author
# (joint) last author

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