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Titolo:
Stavudine resistance: an update on susceptibility following prolonged therapy
Autore:
Lin, PF; Gonzalez, CJ; Griffith, B; Friedland, G; Calvez, V; Ferchal, F; Schinazi, RF; Shepp, DH; Ashraf, AB; Wainberg, MA; Soriano, V; Mellors, JW; Colonno, RJ;
Indirizzi:
Bristol Myers Squibb, Wallingford, CT USA Bristol Myers Squibb Wallingford CT USA yers Squibb, Wallingford, CT USA Yale Univ, Sch Med, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 e Univ, Sch Med, New Haven, CT 06520 USA VA Connecticut Healthcare Syst, W Haven, CT USA VA Connecticut Healthcare Syst W Haven CT USA care Syst, W Haven, CT USA Hop La Pitie Salpetriere, CERVI, Paris, France Hop La Pitie Salpetriere Paris France Salpetriere, CERVI, Paris, France Hop St Louis, Paris, France Hop St Louis Paris FranceHop St Louis, Paris, France Emory Univ, VA Med Ctr, Decatur, GA USA Emory Univ Decatur GA USAEmory Univ, VA Med Ctr, Decatur, GA USA NYU, Sch Med, N Shore Univ Hosp, Manhasset, NY USA NYU Manhasset NY USANYU, Sch Med, N Shore Univ Hosp, Manhasset, NY USA McGill Univ, AIDS Ctr, Montreal, PQ, Canada McGill Univ Montreal PQ Canada Gill Univ, AIDS Ctr, Montreal, PQ, Canada Inst Salud Carlos III, Madrid, Spain Inst Salud Carlos III Madrid SpainInst Salud Carlos III, Madrid, Spain
Titolo Testata:
ANTIVIRAL THERAPY
fascicolo: 1, volume: 4, anno: 1999,
pagine: 21 - 28
SICI:
1359-6535(1999)4:1<21:SRAUOS>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; HIGH-LEVEL RESISTANCE; POL GENE-MUTATIONS; REVERSE-TRANSCRIPTASE; NONNUCLEOSIDE INHIBITORS; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; HIV-1 SENSITIVITY; CONTROLLED TRIAL; DIDANOSINE DDI;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Lin, PF Bristol Myers Squibb, Wallingford, CT USA Bristol Myers Squibb Wallingford CT USA ibb, Wallingford, CT USA
Citazione:
P.F. Lin et al., "Stavudine resistance: an update on susceptibility following prolonged therapy", ANTIVIR TH, 4(1), 1999, pp. 21-28

Abstract

The current report summarizes the available published and unpublished datafrom several investigators on resistance in clinical isolates following prolonged stavudine therapy. Results suggest that stavudine resistance is both modest in degree and infrequent in appearance. Phenotypic evaluation of 61 patients on stavudine therapy showed only modest changes in drug sensitivity following up to 29 months of treatment. The post-treatment isolates from 15 patients exhibited an increase in EC50 value >fourfold (level above variability of assay) when compared with the corresponding pretreatment isolates. However, the vast majority (11) of these pretreatment isolates either had unexpectedly low EC50 levels and/or had post-treatment isolates that lacked any amino acid changes within their reverse transcriptase (RT) gene toaccount for the observed change in sensitivity. Of the four remaining isolates, two appeared to have a multi-resistant phenotype to several nucleoside analogues and two had no detectable RT amino acid changes to account for the observed change in stavudine sensitivity To date. clinical HIV-1 isolates displaying stavudine-specific resistance have yet to be reported. Furthermore, full or partial RT sequence analysis of 194 post-treatment isolates failed to identify any consistent amino acid changes. The strain-specific V75T mutation reported to confer stavudine resistance to the HXB2 HIV-1 strain in vitro, was found in only six isolates and did not correlate with stavudine resistance. This low incidence of stavudine resistance is in strikingcontrast to that observed with other nucleoside analogues and further supports the use of stavudine in first-line combination therapy for HIV patients.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 01:01:17