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Ymittos Athens, Greece

Pingen M.,Erasmus University Rotterdam | Pingen M.,University Utrecht | Wensing A.M.J.,University Utrecht | Fransen K.,Institute of Tropical Medicine | And 9 more authors.
Retrovirology | Year: 2014

Background: In approximately 10% of newly diagnosed individuals in Europe, HIV-1 variants harboring transmitted drug resistance mutations (TDRM) are detected. For some TDRM it has been shown that they revert to wild type while other mutations persist in the absence of therapy. To understand the mechanisms explaining persistence we investigated the in vivo evolution of frequently transmitted HIV-1 variants and their impact on in vitro replicative capacity. Results: We selected 31 individuals infected with HIV-1 harboring frequently observed TDRM such as M41L or K103N in reverse transcriptase (RT) or M46L in protease. In all these samples, polymorphisms at non-TDRM positions were present at baseline (median protease: 5, RT: 6). Extensive analysis of viral evolution of protease and RT demonstrated that the majority of TDRM (51/55) persisted for at least a year and even up to eight years in the plasma. During follow-up only limited selection of additional polymorphisms was observed (median: 1). Conclusions: We demonstrate limited in vivo evolution of protease and RT harbouring frequently observed TDRM in the plasma. This is in line with the high in vitro replication capacity of patient-derived viruses harbouring TDRM compared to site-directed mutant viruses harbouring TDRM. As site-directed mutant viruses have a lower replication capacity than the patient-derived viruses with similar mutational patterns, we propose that (baseline) polymorphisms function as compensatory mutations improving viral replication capacity. © 2014 Pingen et al.; licensee BioMed Central Ltd. Source


Baraboutis I.G.,Evaggelismos General Hospital | Papastamopoulos V.,Evaggelismos General Hospital | Georgiou O.,Evaggelismos General Hospital | Samarkos M.,Evaggelismos General Hospital | And 3 more authors.
International Journal of STD and AIDS | Year: 2010

We report an extreme case of high-grade needlestick exposure of a health-care worker to serum from multiple HIV-infected patients after trying to prematurely remove the respective tubes from an automated biochemical analyser. After review of the medical records of the eight source patients, we offered the health-care worker an expanded postexposure prophylaxis regimen including the entry inhibitor enfuvirtide. She refused to take subcutaneous injections, so we recommended the use of the integrase inhibitor raltegravir. She completed therapy without problems and periodic evaluation for HIV transmission up to nine months after the incident was negative. Source


Pingen M.,University Utrecht | Wensing A.M.J.,University Utrecht | Fransen K.,Institute of Tropical Medicine | De Bel A.,Vrije Universiteit Brussel | And 8 more authors.
Retrovirology | Year: 2015

Background: In approximately 10% of newly diagnosed individuals in Europe, HIV-1 variants harboring transmitted drug resistance mutations (TDRM) are detected. For some TDRM it has been shown that they revert to wild type while other mutations persist in the absence of therapy. To understand the mechanisms explaining persistence we investigated the in vivo evolution of frequently transmitted HIV-1 variants and their impact on in vitro replicative capacity. Results: We selected 31 individuals infected with HIV-1 harboring frequently observed TDRM such as M41L or K103N in reverse transcriptase (RT) or M46L in protease. In all these samples, polymorphisms at non-TDRM positions were present at baseline (median protease: 5, RT: 6). Extensive analysis of viral evolution of protease and RT demonstrated that the majority of TDRM (51/55) persisted for at least a year and even up to eight years in the plasma. During follow-up only limited selection of additional polymorphisms was observed (median: 1). Conclusions: We demonstrate limited in vivo evolution of protease and RT harbouring frequently observed TDRM in the plasma. This is in line with the high in vitro replication capacity of patient-derived viruses harbouring TDRM compared to site-directed mutant viruses harbouring TDRM. As site-directed mutant viruses have a lower replication capacity than the patient-derived viruses with similar mutational patterns, we propose that (baseline) polymorphisms function as compensatory mutations improving viral replication capacity. © 2014 Pingen et al.; licensee BioMed Central Ltd. Source


Beloukas A.,National Retrovirus Reference Center | Magiorkinis E.,National Retrovirus Reference Center | Magiorkinis G.,National Retrovirus Reference Center | Magiorkinis G.,University of Oxford | And 4 more authors.
Virus Research | Year: 2012

Phylogenetic analysis has been extensively used as a tool for the reconstruction of epidemiological relations for research or for forensic purposes. It was our objective to assess the sensitivity of different phylogenetic methods and various phylogenetic programs to reconstruct epidemiological links among HIV-1 infected patients that is the probability to reveal a true transmission relationship. Multiple datasets (90) were prepared consisting of HIV-1 sequences in protease (PR) and partial reverse transcriptase (RT) sampled from patients with documented epidemiological relationship (target population), and from unrelated individuals (control population) belonging to the same HIV-1 subtype as the target population. Each dataset varied regarding the number, the geographic origin and the transmission risk groups of the sequences among the control population. Phylogenetic trees were inferred by neighbor-joining (NJ), maximum likelihood heuristics (hML) and Bayesian methods. All clusters of sequences belonging to the target population were correctly reconstructed by NJ and Bayesian methods receiving high bootstrap and posterior probability (PP) support, respectively. On the other hand, TreePuzzle failed to reconstruct or provide significant support for several clusters; high puzzling step support was associated with the inclusion of control sequences from the same geographic area as the target population. In contrary, all clusters were correctly reconstructed by hML as implemented in PhyML 3.0 receiving high bootstrap support. We report that under the conditions of our study, hML using PhyML, NJ and Bayesian methods were the most sensitive for the reconstruction of epidemiological links mostly from sexually infected individuals. © 2012 Elsevier B.V. Source

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