title: The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase delays the development of resistance to amprenavir and efavirenz in subtype B and C clinical isolates.
abstract: The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), encoding high-level resistance to lamivudine (3TC), results in decreased HIV-1 replicative capacity, diminished RT processivity, and increased RT fidelity in biochemical assays. We assessed the effect of M184V on the development of resistance to the nonnucleoside RT inhibitors efavirenz (EFV) and nevirapine, and to the protease inhibitor amprenavir (APV) in tissue culture. Genotypic analysis revealed differences in EFV resistance-conferring mutations in subtype B (K103N) versus subtype C (V106 M), and the appearance of both was significantly delayed in the M184V-containing variants compared with the wild type (WT). Similarly, there was a marked delay in the emergence of mutations associated with APV resistance (I54 M/L/V) in subtype B viruses harboring M184V compared with paired WT viral isolates.
authors.affiliation: McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, H3T 1E2 Quebec, Canada.
authors.forename: Karidia
authors.initials: K
authors.lastname: Diallo
authors.forename: Bluma
authors.initials: B
authors.lastname: Brenner
authors.forename: Maureen
authors.initials: M
authors.lastname: Oliveira
authors.forename: Daniela
authors.initials: D
authors.lastname: Moisi
authors.forename: Mervi
authors.initials: M
authors.lastname: Detorio
authors.forename: Matthias
authors.initials: M
authors.lastname: Götte
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000480:Alkynes; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology*; D048588:Benzoxazines; D002219:Carbamates; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D005663:Furans; D005814:Genes, Viral; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010078:Oxazines / Q000494:pharmacology*; D010641:Phenotype; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D002219:Carbamates; D003521:Cyclopropanes; D005663:Furans; D010078:Oxazines; D013449:Sulfonamides; C095108:amprenavir; D012194:RNA-Directed DNA Polymerase; C098320:efavirenz