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

BMC Infectious Diseases

Viktor Müller²  Anne-Mieke Vandamme⁸  David AMC van de Vijver¹  Roger Paredes^1,13  Jenny Svärd⁵  Andrea Rosi⁹  Kristel Van Laethem⁸  Ana B Abecasis^1,10  Anders Sönnerborg⁵  Andrea De Luca⁶  Eugen Schülter^1,11  Carlo Torti³  Maurizio Zazzi⁹  Peter MA Sloot⁴  Matthias Assel⁷  István Bartha^1,12 

[1] Erasmus Medical Centre, Erasmus University Rotterdam, Viroscience, Rotterdam, The Netherlands;Research Group of Theoretical Biology and Evolutionary Ecology, Eötvös Loránd University and the Hungarian Academy of Sciences, Budapest, Hungary;Unit of Infectious Diseases, Department of Medical and Surgical Sciences, University “Magna Graecia”, Catanzaro, Italy;Computational Science, The University of Amsterdam, Amsterdam, The Netherlands;Department of Infectious Diseases, Karolinska Institute, Stockholm, Sweden;University Division of Infectious Diseases, Siena University Hospital, Siena, Italy;High Performance Computing Centre, University of Stuttgart, Stuttgart, Germany;Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium;Department of Medical Biotechnologies, University of Siena, Siena, Italy;Centro de Malária e Outras Doenças Tropicais, Unidade de Microbiologia e Unidade de Saúde Pública e Internacional; Instituto de Higiene e Medicina Tropical, Lisboa, Portugal;Institute of Virology, University of Cologne, Cologne, Germany;Swiss Institute of Bioinformatics, Lausanne, Switzerland;Fundacions IrsiCaixa I Lluita contra la SIDA, Universitat Autònoma de Barcelona, Badalona, Spain

关键词: Sequence analysis;    Transmitted drug resistance;    Superinfection;    HIV;   

Others  :  1145392
DOI  :  10.1186/1471-2334-13-537

 received in 2013-07-23, accepted in 2013-10-29,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Bartha et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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Figure 3.

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