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Titolo:
CORRELATION OF RESPONSE TO TREATMENT AND HIV GENOTYPIC CHANGES DURINGPHASE-III TRIALS WITH SAQUINAVIR AND REVERSE-TRANSCRIPTASE INHIBITOR COMBINATION THERAPY
Autore:
RACE E; GILBERT SM; SHELDON JG; ROSE JSL; MOFFATT AR; SITBON G; DISSANAYEKE SR; CAMMACK N; DUNCAN IB;
Indirizzi:
ROCHE DISCOVERY WELWYN,DEPT VIROL,40 BROADWATER RD,VIROL 1 WELWYN GARDEN CIT AL7 3AY HERTS ENGLAND ROCHE DISCOVERY WELWYN,DEPT VIROL WELWYN GARDEN CIT AL7 3AY HERTS ENGLAND PROFESS GENET LAB UPPSALA SWEDEN
Titolo Testata:
AIDS
fascicolo: 12, volume: 12, anno: 1998,
pagine: 1465 - 1474
SICI:
0269-9370(1998)12:12<1465:CORTTA>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEASE INHIBITORS; SEQUENCE DIVERSITY; RESISTANCE; PROTEINASE; INFECTION; VARIANTS; SENSITIVITY; RO-31-8959; MUTATIONS;
Keywords:
HIV PROTEASE; GENOTYPIC CHANGE; THERAPY; COMBINATION; PHENOTYPIC CHANGE; DRUG SENSITIVITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
E. Race et al., "CORRELATION OF RESPONSE TO TREATMENT AND HIV GENOTYPIC CHANGES DURINGPHASE-III TRIALS WITH SAQUINAVIR AND REVERSE-TRANSCRIPTASE INHIBITOR COMBINATION THERAPY", AIDS, 12(12), 1998, pp. 1465-1474

Abstract

Objectives: Assessment of genotypic change in HIV protease during treatment with saquinavir (SQV) in combination with zidovudine (ZDV) and/or zalcitabine (ddC), to determine the influence of such changes on viral phenotype and response to treatment. Design: Virologic substudies of Phase III clinical trials NV14256 and SV14604.Methods: Population sequencing of HIV protease genes amplified from pre- and post-treatmentplasma. Phenotyping of peripheral blood mononuclear cell (PBMC)derived virus isolates, and genotyping of proviral DNA clones amplified fromPBMC used in the expansion of virus isolates. Results: In both trialsthe incidence of Met90 remained at less than or equal to 20% in subjects receiving SQV in combination with ddC (with or without ZDV) for 1 year. A Val48 substitution was observed in two out of 81 subjects after 24 weeks and in two out of 75 subjects after 48 weeks. In 12 out of 13 NV14256 subjects with viral load rebound during SQV monotherapy these substitutions were associated with the rebound. In subjects treatedwith SQV plus ddC, rebound was associated with SQV resistance in six out of 22 cases and ddC resistance in five out of 22 cases. The incidences of non-BRU residues at positions 10, 63 and 71 were increased significantly (P < 0.05, Fisher's exact test) after SQV treatment with orwithout ZDV. However, comparison of genotypic and phenotypic data showed that these changes were not associated with reduced sensitivity toSQV. Conclusions: Virological failure during combination therapy can be due to resistance to either treatment drug, emphasising the need tochange both the reverse transcriptase inhibitor and the protease inhibitor. Only Val48 and Met90 correlated directly with the development of reduced drug sensitivity during treatment with SQV in vivo. (C) Lippincott-Raven Publishers.

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Documento generato il 13/07/20 alle ore 09:44:05