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Titolo:
Thymidine analog and multinucleoside resistance mutations are associated with decreased phenotypic susceptibility to stavudine in HIV type 1 isolatedfrom zidovudine-naive patients experiencing viremia on stavudine-containing regimens
Autore:
Ross, L; Scarsella, A; Raffanti, S; Henry, K; Becker, S; Fisher, R; Liao, QM; Hirani, A; Graham, N; St Clair, M; Hernandez, J;
Indirizzi:
GlaxoSmithKline Inc, Dept Virol, Res Triangle Pk, NC 27709 USA GlaxoSmithKline Inc Res Triangle Pk NC USA 27709 riangle Pk, NC 27709 USA Pacific Oaks Med Ctr, Beverly Hills, CA 90211 USA Pacific Oaks Med Ctr Beverly Hills CA USA 90211 verly Hills, CA 90211 USA Comprehens Care Ctr, Nashville, TN 37232 USA Comprehens Care Ctr Nashville TN USA 37232 e Ctr, Nashville, TN 37232 USA Reg Hosp, St Paul, MN 55101 USA Reg Hosp St Paul MN USA 55101Reg Hosp, St Paul, MN 55101 USA Pacific Horizon Med Grp, San Francisco, CA 94115 USA Pacific Horizon Med Grp San Francisco CA USA 94115 rancisco, CA 94115 USA
Titolo Testata:
AIDS RESEARCH AND HUMAN RETROVIRUSES
fascicolo: 12, volume: 17, anno: 2001,
pagine: 1107 - 1115
SICI:
0889-2229(20010810)17:12<1107:TAAMRM>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE GENE; HIGH-LEVEL RESISTANCE; COMBINATION THERAPY; DIDANOSINE MONOTHERAPY; CONFERRING RESISTANCE; INSERTION MUTATIONS; PROLONGED THERAPY; PLUS DIDANOSINE; POL GENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Ross, L GlaxoSmithKline Inc, Dept Virol, 5 Moore Dr, Res Triangle Pk, NC 27709 USA GlaxoSmithKline Inc 5 Moore Dr Res Triangle Pk NC USA 27709 09 USA
Citazione:
L. Ross et al., "Thymidine analog and multinucleoside resistance mutations are associated with decreased phenotypic susceptibility to stavudine in HIV type 1 isolatedfrom zidovudine-naive patients experiencing viremia on stavudine-containing regimens", AIDS RES H, 17(12), 2001, pp. 1107-1115

Abstract

Studies have demonstrated that HIV-1 isolated from subjects experiencing virologic failure on stavudine (d4T)containing regimens often contains thymidine analog mutations (TAMs), consisting of reverse transcriptase (RT) mutations M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E, previously associated only with zidovudine (ZDV) resistance. In clinical study NZT40012, HIV-1 was isolated from 86 ZDV-naive subjects experiencing viremia on d4T-based therapies (plasma HIV-1 RNA greater than or equal to 1000 copies/ml) and analyzed to examine the association between RT mutations and phenotypic resistance to d4T. Resistance-associated mutations were analyzed from HIV-1 isolated from 85 subjects. Of these, 24 samples (28%) had TAMs, and 30 samples (35%) had either TAMs and/or the Q151M multinucleoside resistance (MNR) mutation. Phenotypic susceptibility to d4T was determined by two commercially available methods. Statistically significant increases (p < 0.001) in phenotypic fold resistance to d4T were observed in virus with at least one TAM or MNR mutation. However, the mean increases in phenotypic resistance were 4-fold for the Antivirogram assay and 3-fold for the Phenosense HIV assay, onlyslightly above the levels used to designate decreased susceptibility to d4T. Subjects can experience viremia on d4T-containing regimens with virus exhibiting only small increases in IC50, suggesting that relatively small changes in viral susceptibility to d4T may influence drug efficacy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 23:02:00