FR AA 0102

Estimating the frequency of superinfection in a large European collaborative HIV database

Presented by István Bartha (Hungary).

I. Bartha¹, M. Assel², P. Sloot³, M. Zazzi⁴, C. Torti⁵, E. Schülter⁶, A. De Luca^7,8, A. Sönnerborg⁹, A.B. Abecasis¹⁰, A.-M. Vandamme^10,11, R. Paredes¹², D. van de Vijver¹³, V. Müller¹, Virolab, EuResist

¹Eotvos Lorand University, Institute of Biology, Budapest, Hungary, ²University of Stuttgart, High Performance Computing Centre, Stuttgart, Germany, ³The University of Amsterdam, Computational Science, Amsterdam, Netherlands, ⁴University of Siena, Department of Molecular Biology, Siena, Italy, ⁵University of Brescia, Institute of Infectious and Tropical Diseases, Brescia, Italy, ⁶University of Cologne, Institute of Virology, Cologne, Germany, ⁷Catholic University of the Sacred Heart, Institute of Clinical Infectious Diseases, Rome, Italy, ⁸Siena University Hospital, Infectious Diseases Unit, Siena, Italy, ⁹Karolinska Institutet, Department of Infectious Diseases, Stockholm, Sweden, ¹⁰Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Lisboa, Portugal, ¹¹Katholieke Universiteit Leuven, Rega Institute for Medical Research, Leuven, Belgium, ¹²Universitat Autònoma de Barcelona, Fundacions IrsiCaixa I Lluita contra la SIDA, Badalona, Spain, ¹³University Medical Centre, Erasmus MC, Deparment of Virology, Rotterdam, Netherlands
 

Background: Superinfection (infection of an HIV positive individual with another virus strain) can facilitate the evolution of HIV by allowing for the recombination of distinct viral lineages. In particular, it might enable the transmission of drug resistant viruses to individuals with drug-sensitive strains who have previously responded well to therapy. We have analyzed routinely collected genotyping data from a large European collaborative HIV database to estimate the frequency of superinfection.
Methods: We used sequence data spanning the protease and partial reverse transcriptase regions from the Virolab and EuResist databases. 4656 patients (gender: male=3140, female=1363, unknown=153; riskgroup: heterosexual=1178, IDU=1073, MSM=951, other=158, unknown=1296) had at least two sequences in the database, with a total of 14196 distinct sequence entries (of which 89.0% belonged to subtype B). Superinfection was indicated when sequences of a patient failed to cluster together in maximum likelihood phylogenetic trees constructed from all available sequences. Putative cases of superinfection were then further investigated with Bayesian phylogenetic methods.
Results: We identified ~300 patients with sequences clustering robustly into at least two distinct lineages (indicative of superinfection) in ML phylogenies; 37 cases represented infection with two distinct subtypes. Bayesian reconstruction of selected subsets of the phylogeny supported ~100 cases of superinfection with high posterior probabilities; support for the remaining cases proved weak to moderate.
Conclusions: Superinfection can occur relatively frequently, and might therefore play an important role in the transmission of drug resistance. We note, however, that our analysis was necessarily confined to patients with at least two available sequences, and might therefore have overestimated the prevalence of superinfection in the general HIV positive population. We have demonstrated that routinely obtained genotyping data can provide sufficient phylogenetic signal to infer superinfection, although further data might be needed to resolve some of the cases.

Links:

• Bartha, et.al. – FRAA0102
• Slides mit Audio
• Präsentation (.ppt)