Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection.

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Ressource 1Download: serval:BIB_543A26F20E1F.P001 (719.77 [Ko])
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Version: author
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It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_543A26F20E1F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Origin of minority drug-resistant HIV-1 variants in primary HIV-1 infection.
Journal
Journal of Infectious Diseases
Author(s)
Metzner K.J., Scherrer A.U., Preiswerk B., Joos B., von Wyl V., Leemann C., Rieder P., Braun D., Grube C., Kuster H., Böni J., Yerly S., Klimkait T., Aubert V., Furrer H., Battegay M., Vernazza P.L., Cavassini M., Calmy A., Bernasconi E., Weber R., Günthard H.F.
Working group(s)
Swiss HIV Cohort Study
Contributor(s)
Aubert V., Barth J., Battegay M., Bernasconi E., Böni J., Bucher HC., Burton-Jeangros C., Calmy A., Cavassini M., Egger M., Elzi L., Fehr J., Fellay J., Furrer H., Fux CA., Gorgievski M., Günthard H., Haerry D., Hasse B., Hirsch HH., Hösli I., Kahlert C., Kaiser L., Keiser O., Kovari H., Kouyos R., Ledergerber B., Martinetti G., Martinez de Tejada B., Metzner K., Müller N., Nadal D., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schöni-Affolter F., Schüpbach J., Speck R., Taffé P., Tarr P., Telenti A., Trkola A.
ISSN
1537-6613 (Electronic)
ISSN-L
0022-1899
Publication state
Published
Issued date
2013
Volume
208
Number
7
Pages
1102-1112
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
BACKGROUND: Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)-naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven.
METHODS: MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters.
RESULTS: Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1-infected patients (8.2% vs 2.5%; P = .004).
CONCLUSIONS: Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin-transmission vs sporadic appearance-of these variants determines their impact on ART needs to be further explored.
Keywords
Adolescent, Adult, Aged, Alleles, Cluster Analysis, Cohort Studies, Drug Resistance, Viral, Female, Genetic Variation, HIV Infections/transmission, HIV Infections/virology, HIV-1/drug effects, HIV-1/genetics, Humans, Male, Middle Aged, Phylogeny, Polymerase Chain Reaction, Sequence Analysis, DNA, Switzerland, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
08/10/2013 17:59
Last modification date
25/09/2019 7:09
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