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.
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.
Diallo
Karidia
K
McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, H3T 1E2 Quebec, Canada.
Brenner
Bluma
B
Oliveira
Maureen
M
Moisi
Daniela
D
Detorio
Mervi
M
Götte
Matthias
M
Wainberg
Mark A
MA
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*
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