Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group.
Abstract: Among the 39 subjects, 18 (46%) developed mutations: one developed the Val75Thr/Ala mutation, four (10%) developed a Gln151Met multidrug-resistance mutation (MDR), associated in one of them with the Phe77Leu and the Phe116Tyr MDR mutations and 14 (36%) developed one or more zidovudine-specific mutations (Met41Leu, Asp67Asn, Lys70Arg, Leu210Trp, Thr215Tyr/Phe).
The reverse transcriptase codon 69 insertion is observed in nucleoside reverse transcriptase inhibitor-experienced HIV-1-infected individuals, including those without prior or concurrent zidovudine therapy.
Abstract: CONCLUSIONS: Six-basepair insertions occurred in virus from 4 of 121 (3%) NRTI-experienced subjects, including those without prior ZDV treatment, and was observed in the absence of the T215Y mutation.
Drug resistance mutations among HIV-1 strains from antiretroviral-naive patients in Martinique, French West Indies.
PMID: 10634203
1999
Journal of acquired immune deficiency syndromes (1999)
Abstract: One carried both mutations T215Y and M41L known to confer a high degree of phenotypic resistance to ZDV.
Abstract: ZDV resistance mutations T215Y/F, M41L, and K70R were found in 2, 5, and 12 individuals, respectively.
HIV resistance to zidovudine: the role of pyrophosphorolysis.
Abstract: The potential replication deficit of an increased reverse reaction during DNA synthesis is compensated by increased DNA synthesis processivity, a phenotype that results from the T215F/Y/K219Q mutations in RT.
Abstract: While this resistance could be unequivocally correlated with multiple mutations in HIV reverse transcriptase (D67N, K70R, T215F/Y, K219Q), the mechanism or phenotype for this resistance has remained obscure for more than a decade, despite active investigation.
Codon 215 mutations in human immunodeficiency virus-infected pregnant women. Swiss Collaborative 'HIV and Pregnancy' Study.
PMID: 9952382
1999
The Journal of infectious diseases
Abstract: Six women (9.6%) harbored a codon T215Y/F mutation, which is associated with high-level resistance to zidovudine.
Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates.
Abstract: To explore this subject further, we have used an endogenous RT reaction to study mutated viruses containing M184V alone or M184V combined with each of the K65R, E89G or both the M41L and T215Y substitutions.
Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants.
Abstract: Overgrowth of these variants suggests that they have better fitness than the original T215Y variant.
Abstract: Sequences of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) domain were determined by direct sequencing of HIV-1 RNA in successive plasma samples from eight seroconverting patients infected with virus bearing the T215Y/F amino acid substitution associated with zidovudine (ZDV) resistance.
Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro.
Abstract: The order of relative fitness was wild type > K70R >> T215Y = M41L+T215Y > M41L.
Abstract: These variants were engineered to contain commonly observed zidovudine resistance mutations in the HIV-1 reverse transcriptase (M41L, K70R, T215Y, and M41L+T215Y).
3'-Azido-3'-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type 1 variants.
Abstract: In addition, the presence of AZT also causes viruses containing the M41L and T215Y substitutions to have diminished sensitivity to other nucleoside analogs (i.e., ddC, ddI, and d4T).
Abstract: Our results suggest that the use of AZT may be contraindicated in those patients for whom resistance to this compound (M41L and/or T215Y) has been demonstrated.
Abstract: This AZT-mediated cross-resistance may help to explain the virological failure of treatment regimens that included ddI plus AZT or ddC plus AZT in situations in which the T215Y and/or M41L mutations were present (F.
Abstract: Through use of PCR amplifications, we discovered an AZT-mediated stimulation of reverse transcription by AZT-resistant viruses carrying the
Genotypic changes in human immunodeficiency virus type 1 associated with loss of suppression of plasma viral RNA levels in subjects treated with ritonavir (Norvir) monotherapy.
Abstract: The relative fitness of the protease V82A ritonavir resistance mutation and reverse transcriptase T215Y/F zidovudine resistance mutation following drug withdrawal were estimated to be 96 to 98% that of the wild type.
HIV mutation literature information.
PMID: 
1999
AIDS (London, England)
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