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Titolo:
DEVELOPMENT OF HIV-1 RESISTANCE TO (-)2'-DEOXY-3'-THIACYTIDINE IN PATIENTS WITH AIDS OR ADVANCED AIDS-RELATED COMPLEX
Autore:
WAINBERG MA; SALOMON H; GU ZX; MONTANER JSG; COOLEY TP; MCCAFFREY R; RUEDY J; HIRST HM; CAMMACK N; CAMERON J; NICHOLSON W;
Indirizzi:
MCGILL UNIV,JEWISH GEN HOSP,CTR AIDS,3755 COTE STE CATHERINE RD MONTREAL PQ H3T 1E2 CANADA UNIV BRITISH COLUMBIA,ST PAULS HOSP,AIDS RES PROGRAM VANCOUVER BC CANADA BOSTON CITY HOSP,HEMATOL SECT BOSTON MA 02118 BOSTON CITY HOSP,ONCOL SECT BOSTON MA 02118 BOSTON CITY HOSP,DEPT MED,CLIN AIDS PROGRAM BOSTON MA 02118 BOSTON UNIV,SCH MED BOSTON MA 02118 GLAXO RES INST RES TRIANGLE PK NC 00000 GLAXO GRP RES LTD GREENFORD UB6 0HE MIDDX ENGLAND
Titolo Testata:
AIDS
fascicolo: 4, volume: 9, anno: 1995,
pagine: 351 - 357
SICI:
0269-9370(1995)9:4<351:DOHRT(>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; HIGH-LEVEL RESISTANCE; REVERSE-TRANSCRIPTASE; CELL-CULTURE; 2'-DEOXY-3'-THIACYTIDINE BCH-189; REPLICATION INVITRO; ZIDOVUDINE; TYPE-1; MUTATION; SENSITIVITY;
Keywords:
DRUG RESISTANCE; (-)2'-DEOXY-3'-THIACYTIDINE; CLINICAL TRIAL; CODON 184; VIRAL GENOTYPE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
M.A. Wainberg et al., "DEVELOPMENT OF HIV-1 RESISTANCE TO (-)2'-DEOXY-3'-THIACYTIDINE IN PATIENTS WITH AIDS OR ADVANCED AIDS-RELATED COMPLEX", AIDS, 9(4), 1995, pp. 351-357

Abstract

Objective: To determine the rate of development of in vitro HIV resistance to (-)2'-deoxy-3'-thiacytidine (3TC) and relate the effect of dose to emergence of resistance. Methods: HIV-infected men and non-pregnant women, aged greater than or equal to 18 years, with a CD4 count less than or equal to 300x10(6)/I cells were followed in a Phase I/II study, in which they were evaluated for tolerance to 3TC and effect of this agent with regard to viral susceptibility. Peripheral blood and plasma samples were collected at regular intervals for analysis. HIV wasisolated using umbilical cord blood mononuclear cells as targets. These cells were also used in determinations of median inhibitory drug concentration. Specific amplification of the 184 mutation site, associated with HIV resistance to 3TC, was performed by polymerase chain reaction, using specific primer pairs, on DNA harvested from infected peripheral blood mononuclear cells (PBMC) of donors or, alternatively, on DNA that had been reverse transcribed from plasma-associated HIV RNA. Results: Phenotypic resistance was detected in approximately one-third of individuals studied, who were followed between 8 and 56 weeks. Development of 3TC resistance occurred independently of dose, although time of first appearance of resistant HIV-1 variants appeared reduced at high 3TC doses. Amino-acid changes at codon 184 in HIV-1 reverse transcriptase were associated with, and preceded, the development of phenotypic 3TC resistance. Most commonly, a Met to Ile substitution appearedtransiently before being superceded by a Val substitution at codon 184. Conclusions: In vitro resistance to 3TC developed in a high proportion of subjects who received prolonged monotherapy with this drug. Thedevelopment of resistance to 3TC was associated with appearance of mutated viral forms and the disappearance of wild-type virus, with regard to codon 184, in both patient plasma and PBMC.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 20:57:50