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

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Mar 21, 2024 200 likes •374 views

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

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CRF01_AE: Do we need a customized CCR5 antagonist treatment recommendation?

Nico Pfeifer Max Planck Insitute for Informatics

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HIV coreceptor usage

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HIV coreceptor usage

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HIV coreceptor usage

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HIV coreceptor usage

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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?

CRF01_AE update

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Could be confounded

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

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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

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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

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Genetic tropism test

1. Lengauer et al. 2007, Nature Biotechnol.
2. Pfeifer and Lengauer 2012, Bioinformatics

Standard geno2pheno[coreceptor] version [1] New geno2pheno-C_NGS-Sanger version [2]

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Geno2pheno-C_NGS-Sanger

Training Prediction

Pfeifer and Lengauer 2012, Bioinformatics

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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

Could be improved?

1. Lengauer et al. 2007, Nature Biotechnol.
2. Pfeifer and Lengauer 2012, Bioinformatics

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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

ld calls

– Need more samples for intermediate range

Current results

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Thanks to …

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

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