Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group.
AIDS
; 13(13): 1705-9, 1999 Sep 10.
Article
em En
| MEDLINE
| ID: mdl-10509572
ABSTRACT
OBJECTIVE:
Assessment of genotypic changes in the reverse transcriptase gene of HIV-1 occurring in antiretroviral naive patients treated by stavudine plus didanosine combination therapy.METHODS:
Sequence analysis (codons 1-230) was performed after amplification of the reverse transcriptase gene from plasma samples collected at baseline and at the end of treatment from 39 previously treatment-naive patients treated for 24-48 weeks.RESULTS:
At baseline, mutations associated with zidovudine resistance were detected in plasma from two patients Asp67Asn/Lys219Gln and Leu210Trp. Among the 39 subjects, 18 (46%) developed mutations one developed the Val75Thr/Ala mutation, four (10%) developed a Gln151Met multidrug-resistance mutation (MDR), associated in one of them with the Phe77Leu and the Phe116Tyr MDR mutations and 14 (36%) developed one or more zidovudine-specific mutations (Met41Leu, Asp67Asn, Lys70Arg, Leu210Trp, Thr215Tyr/Phe). The development of a Met41Leu zidovudine-specific mutation was associated with the development of a Gln151Met mutation in one patient. Other reverse transcriptase mutations known to confer resistance to nucleoside analogues were not detected. At inclusion, there was no statistical difference in HIV-1 load between patients who developed resistance mutations and those who did not. RNA HIV-1 load decrease was higher (P = 0.05) in patients who maintained a wild-type reverse transcriptase genotype (-2.22 log10 copies/ml) than in patients who developed resistance mutations (-1.14 log10 copies/ml).CONCLUSION:
Stavudine/didanosine combination therapy is associated with emergence of zidovudine-related resistance or MDR mutations in naive patients. These findings should be considered when optimizing salvage therapy for patients who have received a treatment including stavudine/didanosine combination.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Zidovudina
/
Infecções por HIV
/
Didanosina
/
Estavudina
/
Resistência a Múltiplos Medicamentos
/
Inibidores da Transcriptase Reversa
/
Fármacos Anti-HIV
/
Transcriptase Reversa do HIV
/
Mutação
Limite:
Adult
/
Humans
Idioma:
En
Revista:
AIDS
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
França