Universität zu Köln

Bartha, Istvan ORCID: 0000-0003-3360-1999, Assel, Matthias, Sloot, Peter M. A., Zazzi, Maurizio ORCID: 0000-0002-0344-6281, Torti, Carlo, Schuelter, Eugen, De Luca, Andrea ORCID: 0000-0002-9561-9193, Sonnerborg, Anders ORCID: 0000-0001-8928-3374, Abecasis, Ana B., Van Laethem, Kristel ORCID: 0000-0001-6036-2271, Rosi, Andrea, Svard, Jenny, Paredes, Roger, van de Vijver, David A. M. C., Vandamme, Anne-Mieke ORCID: 0000-0002-6594-2766 and Mueller, Viktor (2013). Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort. BMC Infect. Dis., 13. LONDON: BMC. ISSN 1471-2334

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bartha, Istvan UNSPECIFIED orcid.org/0000-0003-3360-1999 UNSPECIFIED Assel, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Sloot, Peter M. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zazzi, Maurizio UNSPECIFIED orcid.org/0000-0002-0344-6281 UNSPECIFIED Torti, Carlo UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuelter, Eugen UNSPECIFIED UNSPECIFIED UNSPECIFIED De Luca, Andrea UNSPECIFIED orcid.org/0000-0002-9561-9193 UNSPECIFIED Sonnerborg, Anders UNSPECIFIED orcid.org/0000-0001-8928-3374 UNSPECIFIED Abecasis, Ana B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Laethem, Kristel UNSPECIFIED orcid.org/0000-0001-6036-2271 UNSPECIFIED Rosi, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Svard, Jenny UNSPECIFIED UNSPECIFIED UNSPECIFIED Paredes, Roger UNSPECIFIED UNSPECIFIED UNSPECIFIED van de Vijver, David A. M. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vandamme, Anne-Mieke UNSPECIFIED orcid.org/0000-0002-6594-2766 UNSPECIFIED Mueller, Viktor UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-472019
DOI:	10.1186/1471-2334-13-537
Journal or Publication Title:	BMC Infect. Dis.
Volume:	13
Date:	2013
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-2334
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VIRUS TYPE-1 SUPERINFECTION; PRIMARY INFECTION; VIRAL LOAD; RECOMBINATION; TRANSMISSIONS; PERSISTENCE; MUTATIONS; EVOLUTION; ALIGNMENT; PROTEASE Multiple languages Infectious Diseases Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47201