Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients.

Details

Ressource 1Download: REF.pdf (1235.23 [Ko])
State: Public
Version: Final published version
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_28964C6A0253
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients.
Journal
Clinical Infectious Diseases
Author(s)
Metzner K.J., Giulieri S.G., Knoepfel S.A., Rauch P., Burgisser P., Yerly S., Günthard H.F., Cavassini M.
ISSN
1537-6591
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
48
Number
2
Pages
239-247
Language
english
Abstract
BACKGROUND: Early virological failure of antiretroviral therapy associated with the selection of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients is very critical, because virological failure significantly increases the risk of subsequent failures. Therefore, we evaluated the possible role of minority quasispecies of drug-resistant human immunodeficiency virus type 1, which are undetectable at baseline by population sequencing, with regard to early virological failure. METHODS: We studied 4 patients who experienced early virological failure of a first-line regimen of lamivudine, tenofovir, and either efavirenz or nevirapine and 18 control patients undergoing similar treatment without virological failure. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. RESULTS: Before treatment, none of the viruses showed any evidence of drug resistance in the standard genotype analysis. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. In contrast, all 4 patients whose treatment was failing had harbored drug-resistant viruses at low frequencies before treatment, with a frequency range of 0.07%-2.0%. A range of 1-4 mutations was detected in viruses from each patient. Most of the minority quasispecies were rapidly selected and represented the major virus population within weeks after the patients started antiretroviral therapy. All 4 patients showed good adherence to treatment. Nonnucleoside reverse-transcriptase inhibitor plasma concentrations were in normal ranges for all 4 patients at 2 separate assessment times. CONCLUSIONS: Minority quasispecies of drug-resistant viruses, detected at baseline, can rapidly outgrow and become the major virus population and subsequently lead to early therapy failure in treatment-naive patients who receive antiretroviral therapy regimens with a low genetic resistance barrier.
Keywords
Adenine, Alleles, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Benzoxazines, Drug Resistance, Viral, Female, Genotype, HIV Infections, HIV Reverse Transcriptase, HIV-1, Humans, Lamivudine, Male, Medication Adherence, Mutation, Missense, Nevirapine, Phosphonic Acids, Plasma, Polymerase Chain Reaction, Selection (Genetics), Treatment Failure
Pubmed
Web of science
Open Access
Yes
Create date
05/03/2009 13:26
Last modification date
14/02/2022 7:54
Usage data