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Titolo:
Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine
Autore:
Coakley, EP; Gillis, JM; Hammer, SM;
Indirizzi:
Beth Israel Deaconess Med Ctr, Dept Med, Div Infect Dis, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr Boston MA USA 02215 s, Boston, MA 02215 USA Harvard Med Sch, Boston, MA USA Harvard Med Sch Boston MA USAHarvard Med Sch, Boston, MA USA Columbia Univ Coll Phys & Surg, Dept Med, Div Infect Dis, New York, NY USAColumbia Univ Coll Phys & Surg New York NY USA ect Dis, New York, NY USA
Titolo Testata:
AIDS
fascicolo: 2, volume: 14, anno: 2000,
pagine: F9 - F15
SICI:
0269-9370(20000128)14:2<F9:PAGRPO>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYPE-1 REVERSE-TRANSCRIPTASE; DRUG SUSCEPTIBILITY; MONOTHERAPY; ZIDOVUDINE; THERAPY; MUTATIONS; STRAINS; ASSAY;
Keywords:
didanosine; stavudine; resistance;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Coakley, EP Beth Israel Deaconess Med Ctr, Dept Med, Div Infect Dis, 1 Deaconess Rd, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr 1 Deaconess Rd Boston MA USA 02215
Citazione:
E.P. Coakley et al., "Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine", AIDS, 14(2), 2000, pp. F9-F15

Abstract

Objective: To evaluate the phenotypic susceptibilities and genotypic resistance patterns to both didanosine and stavudine of baseline and follow-up HIV-1 isolate pairs, derived from antiretroviral naive subjects treated withthis dual nucleoside combination. Design and methods: Phenotypic drug susceptibility testing was performed in peripheral blood mononuclear cells on 34 viral isolate pairs derived frompatients participating in the EMS AI-460 trial. Sequencing of the completereverse transcriptase of 36 study isolate pairs, baseline and follow-up, was performed using standard dideoxy techniques. Results: The mean fold change in susceptibilities to didanosine was 1.6 (P= 0.278) and to stavudine 1.9 (P = 0.002, Wilcoxon's signed rank lest). Mutations classically associated with zidovudine resistance were observed to emerge in 7 out of 36 isolates, T215Y/F (four), M41L + T215Y/F (two) and D67N tone). Other mutations observed included the A62V, V751, F77L, F116Y, Q151M multinucleoside resistance complex (one), the Q151M mutation (two) and the rare V75T mutation (two). No mutations classically associated with didanosine exposure and resistance were observed. No relationship was evident between the emergence of zidovudine associated mutations and the level of phenotypic resistance to either stavudine or didanosine or between the emergence of zidovudine associated mutations and changes in plasma HIV RNA levels. Conclusion: These comprehensive data demonstrate modest (( twofold) mean reductions in didanosine and stavudine susceptibilities at follow-up. The emergence of zidovudine associated mutations in this retroviral-naive population treated with combination didanosine and stavudine therapy is notable. Furthermore, the emergence of these mutations and of the Q151M multinucleoside resistance complex raise concerns for potential nucleoside analog cross-resistance. The potential mechanisms driving the selection of the zidovudine associated mutations in the setting of didanosine and stavudine therapy and the relevance of these findings to current three and four drug regimens merit further evaluation. (C) 2000 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 01:13:33