Zidovudine resistance predicted by direct detection of mutations in DNA from HIV-infected lymphocytes

Larder, Brendan A.; Kellam, Paul; Kemp, Sharon D.

doi:10.1097/00002030-199102000-00002

Cited by 262 publications

(187 citation statements)

References 0 publications

Supporting

Mentioning

182

Contrasting

Order By: Relevance

“…The Lys-70-to-Arg mutation causes an eightfold decrease in AZT susceptibility without affecting ddC susceptibility (13,15), whereas we have shown that the Thr-69-to-Asp mutation causes a comparable decrease in ddC susceptibility without affecting AZT susceptibility. The lack of cross-resistance is encouraging with regard to the potential usefulness of combination therapy to delay or prevent outgrowth of resistant virus.…”

Section: Discussioncontrasting

confidence: 59%

“…The Asp-69 mutation may be a step toward development of higher-level resistance; evidence to this effect exists for the AZT resistance mutations involving amino acid residues 70 and 215 (15,16). There may also be mutations conferring additional ddC resistance in portions of the gene which were not included in the PCR products amplified from our patient.…”

Section: Discussionmentioning

confidence: 94%

“…We infer that Ile-165 is unrelated to ddC resistance. This is based partly on comparison with AZT resistance mutations, which tend to be additive or synergistic (15). In addition, Ile-165, unlike other resistance mutations thus far characterized (15,27) …”

Section: Discussionmentioning

confidence: 99%

“…These viruses were found to contain up to five mutations (four amino acid substitutions) in the pol gene of HIV (16). Other studies have now confirmed that HIV regularly acquires resistance during AZT therapy (3,12,24) and that this resistance is associated with the presence of one or more of these mutations (3,15,17).…”

mentioning

confidence: 92%

See 3 more Smart Citations

Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine

Fitzgibbon

Howell

Haberzettl

et al. 1992

Antimicrob Agents Chemother

185

104

View full text Add to dashboard Cite

To investigate whether human immunodeficiency virus type 1 pol gene mutations are selected during prolonged 2',3'-dideoxycytidine (ddC) therapy, we used the polymerase chain reaction to amplify a portion of the reverse transcriptase segment of the pol gene from the peripheral blood mononuclear cell DNA of a patient with AIDS before and after an 80-week course of ddC therapy. The consensus sequence from the second sample contained a unique double mutation (ACT to GAT) in the codon for reverse transcriptase amino acid 69, causing substitution of aspartic acid (Asp) for the wild-type threonine (Thr). A mutation (ACA to ATA) also occurred in the codon for position 165, causing substitution of isoleucine (Ile) for Thr. The GAT (Asp) codon was introduced into the pol gene of a molecular clone of human immunodeficiency virus via site-directed mutagenesis. Following transfection, mutant and wild-type viruses were tested for susceptibility to ddC by a plaque reduction assay. The mutant virus was fivefold less susceptible to ddC than the wild type; crossresistance to 3'-azido-3'-deoxythymidine or 2'3'-dideoxyinosine was not found. The lle-165 mutation did not confer additional ddC resistance. The Asp-69 substitution may have contributed to the generation of resistant virus in this patient.

show abstract

Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

See 2 more Smart Citations

Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine

Fitzgibbon

Howell

Haberzettl

et al. 1992

Antimicrob Agents Chemother

185

104

View full text Add to dashboard Cite

show abstract

“…Assays for drug resistance testing in HIV-1 infection are available detecting mutations that confer phenotypic resistance, either by genotyping all relevant codons or by hybridization-based detection of selected codons (Larder et al 1991, Kozal et al 1993. Interpretation of results can be done according to different guidelines, all of them based on appropriate criteria (Durant et al 1999).…”

mentioning

confidence: 99%