CRF01_AE: Do we need a customized CCR5 antagonist treatment - PowerPoint PPT Presentation

CRF01_AE: Do we need a customized CCR5 antagonist treatment recommendation? Nico Pfeifer Max Planck Insitute for Informatics

HIV coreceptor usage

HIV coreceptor usage

HIV coreceptor usage

HIV coreceptor usage

CRF01_AE update • Recent papers report high proportions of X4- capable CRF01_AE infected patients – Mulinge et al. 2013, PLoS ONE – Wai-Chi To et al. 2013, AIDS Res Hum Retroviruses. • Overestimation of X4-capable or other reasons?

Could be confounded http://www.hivviralload.com/blog/2008/11/25/the-hiv-subtype-picture.html

Genetic tropism test Adapted from: T. Lengauer, N. Pfeifer, and R. Kaiser Personalized HIV therapy to control drug resistance Drug Discovery Today: Technologies 2014, 11, pp 57-64

Genetic tropism test Adapted from: T. Lengauer, N. Pfeifer, and R. Kaiser Personalized HIV therapy to control drug resistance Drug Discovery Today: Technologies 2014, 11, pp 57-64

Genetic tropism test Standard geno2pheno[coreceptor] version [1] New geno2pheno-C_NGS-Sanger version [2] 1. Lengauer et al. 2007, Nature Biotechnol. 2. Pfeifer and Lengauer 2012, Bioinformatics

Geno2pheno-C_NGS-Sanger Training Prediction Pfeifer and Lengauer 2012, Bioinformatics

Could be improved? • Collaboration with Nagoya Medical Center (Japan) and Klimkait et al. (InPheno, Uni Basel) – 297 V3 loop sequences of CRF01_AE – Discordance between standard geno2pheno[coreceptor] [1] and new version [2] for certain cases (X4-capable / R5) – Selected 21 samples with largest discordance as well as 5 samples with X4 agreement (control) – PhenXR phenotypes measured in Basel 1. Lengauer et al. 2007, Nature Biotechnol. 2. Pfeifer and Lengauer 2012, Bioinformatics

Current results • 17 samples successfully phenotyped – 14/15 calls with X4-capable / R5 (old / new G2P) were phenotyped as R5 (the other one was mixed-dual according to PhenXR) – Only 2 of the X4/X4 calls could be phenotyped (both R5 according to PhenXR) • Conclusions – It seems as if calling CRF01_AEs R5 when new tool confidently calls it R5 is better than using the old calls – Need more samples for intermediate range

Thanks to … Thomas Lengauer Rolf Kaiser Thomas Klimkait Séverine Louvel Wataru Sugiura Masakazu Matsuda Yoshiyuki Yokomaku

Thanks to … Thomas Lengauer Rolf Kaiser Thomas Klimkait Séverine Louvel Wataru Sugiura Masakazu Matsuda Yoshiyuki Yokomaku