HIV‐1 biological phenotype and the development of zidovudine resistance in relation to disease progression in asymptomatic individuals during treatment
作者:
Charles Boucher,
Joep Lange,
Frank Miedema,
Gerrit Weverling,
Maarten Koot,
Jan Mulder,
Jaap Goudsmit,
Paul Kellam,
Brendan Larder,
Matthijs Tersmette,
期刊:
AIDS
(OVID Available online 1992)
卷期:
Volume 6,
issue 11
页码: 1259-1264
ISSN:0269-9370
年代: 1992
出版商: OVID
关键词: HIV;AIDS;zidovudine;zidovudine resistance;HIV-1 biological phenotype;MT-2 cell assay
数据来源: OVID
摘要:
ObjectiveTo determine which parameters are associated with clinical progression during zidovudine treatment of asymptomatic HIV-1-infected individuals.MethodsTwenty-four initially asymptomatic HIV-1-infected individuals were treated with zidovudine and followed until the development of AIDS or for approximately 3 years. HIV-1 phenotype was determined by cocultivation of patient cells with donor lymphocytes, and by a new assay of direct cocultivation with MT-2 cells. Specific mutations in the HIV-1 reverse transcriptase (RT) gene conferring resistance to zidovudine were detected using a selective polymerase chain reaction.ResultsProgression to AIDS was more rapid in individuals harbouring syncytium-inducing (SI) viral isolates or showing a conversion from non-syncytium-inducing (NSI) to SI viral isolates. One out of 20 patients who spent a total of 559 months harbouring an NSI phenotype progressed to AIDS, whereas eight out of 12 patients who spent a total of 223 months harbouring an SI phenotype progressed to AIDS (P<0.001). There was no significant difference between SI and non-SI isolates in the frequency of five mutations causing zidovudine resistance. However, all SI isolates obtained after 2 years of treatment contained mutations in codons 41 and 215 of the RT gene, whereas only five out of 11 (45%) NSI isolates obtained at that time had this combination of mutations.ConclusionsConversion to the SI phenotype cannot be prevented by zidovudine treatment. The presence or appearance of an SI virus heralded disease progression in zidovudine-treated individuals. Further research is required to investigate the relationship between virus phenotype and development of zidovudine resistance.
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