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Title: Multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 strains isolated from patients from different European countries
Authors: Schmit, J C ×
Van Laethem, Kristel
Ruiz, L
Hermans, P
Sprecher, S
Sönnerborg, A
Leal, M
Harrer, T
Clotet, B
Arendt, V
Lissen, E
Witvrouw, Myriam
Desmyter, Jan
De Clercq, Erik
Vandamme, Anne-Mieke #
Issue Date: Oct-1998
Publisher: Gower Academic Journals
Series Title: AIDS vol:12 issue:15 pages:2007-15
Abstract: OBJECTIVE: To study the prevalence of multiple dideoxynucleoside (ddN)-resistant (MddNR) HIV-1 in European patients under treatment with multiple ddN analogues, and to characterize MddNR strains genotypically and phenotypically. DESIGN AND METHODS: Blood samples from patients after > or = 6 months of treatment with multiple ddN were screened for the MddNR mutation Q151M. After confirmation of MddNR in 15 patients from five European countries, genotypic resistance was evaluated by DNA sequencing of the reverse transcriptase (RT) gene. Phenotypic resistance was measured by the recombinant virus assay. Results were compared with the clinical evolution of the patients. RESULTS: The prevalence of MddNR strains in European patients treated with multiple ddN analogues was 3.5%. Viruses typically contained amino acid substitutions V75F, F77L, F116Y and Q151M in the RT gene. A new mutation, S68G, was frequently associated with MddNR. Phenotypically, viruses displayed high-level resistance to zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), stavudine (d4T) and partial resistance to lamivudine (3TC) once multiple mutations were present. Under in-vivo treatment pressure, some MddNR strains additionally developed resistance to protease inhibitors or non-nucleoside RT inhibitors (NNRTI). Clinically, most patients had advanced HIV disease with low CD4 cell counts, high viral loads and a rapid progression, but two patients harbouring MddNR virus responded well to dual protease inhibitor associations. CONCLUSIONS: MddNR resistant HIV-1 can be found in European patients. MddNR is characterized by a specific set of drug resistance mutations, cross-resistance to most ddN analogues and a fast clinical progression. MddNR can be associated with protease inhibitor or NNRTI resistance.
ISSN: 0269-9370
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Laboratory of Clinical and Epidemiological Virology (Rega Institute)
Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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