Kinetics of HIV-1 RNA and resistance-associated mutations after cessation of antiretroviral combination therapy
作者:
Markus Birk,
Veronica Svedhem,
Anders Sönnerborg,
期刊:
AIDS
(OVID Available online 2001)
卷期:
Volume 15,
issue 11
页码: 1359-1368
ISSN:0269-9370
年代: 2001
出版商: OVID
关键词: Antiretroviral therapy;drug resistance;HIV-1;rebound;viral load
数据来源: OVID
摘要:
ObjectiveTo study the kinetics of HIV-1 RNA and drug-induced mutations after cessation of antiretroviral therapy (ART).Design and methodsSuccessive plasma samples from 26 patients were tested for HIV-1 RNA by PCR and for mutations associated with drug resistance by sequencing of thepolgene.ResultsAfter cessation of ART the phase of undetectable virus (< 50 copies/ml), ranging from 6 to more than 29 days, was followed by a rapid viral increase, which slowed down before a plateau corresponding to pre-treatment levels or higher was reached in most cases (14/19 patients). In one patient virus was still undetectable at 4 weeks. Also, a significantly larger number of primary protease inhibitor (PI)-associated mutations reverted to wild-type, as compared with secondary PI-, and primary reverse transcriptase inhibitor (RTI)-associated mutations. During the rapid viral increase no mutations disappeared, which instead happened during the slower viral increase preceding the viral plateau level.ConclusionAfter discontinuation of ART large individual variations were found for the time period until HIV-1 became detectable in plasma, possibly due to differences in the HIV-1 specific immunity. The more rapid loss of primary PI mutations suggests that they might cause a more impaired viral fitness than primary RTI mutations. However, the persistence of drug mutations during the initial viral load increase indicates that mutated strains may still replicate efficiently.
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