Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort.

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_148CAA34EC7C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort.
Périodique
Bmc Infectious Diseases
Auteur(s)
Bartha I., Assel M., Sloot P.M., Zazzi M., Torti C., Schülter E., Luca A.D., Sönnerborg A., Abecasis A.B., Van Laethem K., Rosi A., Svärd J., Paredes R., van de Vijver D.A., Vandamme A.M., Müller V.
ISSN
1471-2334 (Electronic)
ISSN-L
1471-2334
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
13
Pages
537
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish
Résumé
BACKGROUND: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients.
METHODS: We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples.
RESULTS: 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching. Drug resistance increased in this single patient.
CONCLUSIONS: Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation. Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route. We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment.
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/02/2014 19:45
Dernière modification de la notice
20/08/2019 13:43
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