Abstract
The development of HIV coreceptor antagonists—such as maraviroc—has made coreceptor use diagnosis mandatory for each patient in the clinical setting. Technical issues presented by Trofile™, the gold standard phenotypic assay, hindered its use as a routine diagnostic tool. This issue has lead to the development of genotypic algorithms, whose evaluations are based on V3 region sequences of the viral envelope. These algorithms proved to be cheaper, easier to use, and less time consuming than the phenotypic method. One of them, geno2pheno has also gained widespread use since it showed 86.5% concordance with the gold-standard phenotypic assay. In this regard, the present project aims to develop accurate predictive models based on V3 sequence information. For this, 2,109 DNA sequences from HIV-1 subtype B were used. Data labeled with geno2pheno’s results were used to construct and evaluate the logistic regression models. Three parsimonious models were obtained, and their evaluations showed promising results. These outcomes encourage us to continue the project of an easy to use and more accurate alternative for HIV coreceptor use diagnosis, capable of guiding clinical decision making regarding the use of CCR5 antagonists in HIV treatment.
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References
Deng, H., Liu, R., Ellmeier, W., et al.: Identification of a major co-receptor for primary isolates of HIV-1. Nature 381(6584), 661–666 (1996)
Dragic, T., Litwin, V., Allaway, G., et al.: HIV-1 entry into CD4R cells is mediated by the chemokine receptor CC-CKR-5. Nature 381(6584), 667–673 (1996)
Maeda, K., Nakata, H., Ogata, H., et al.: The current status of, and challenges in, the development of CCR5 inhibitors as therapeutics for HIV-1 infection. Curr. Opin. Pharmacol. 4(5), 447–452 (2004)
Seibert, C., Sakmar, T.: Small-molecule antagonists of CCR5 and CXCR4: a promising new class of anti-HIV drugs. Curr. Pharm. Des. 10(17), 2041–2062 (2004)
Anonymous: FDA approves maraviroc tablets. AIDS Patient Care STDS 21(9), 702 (2007)
Poveda, E., Alcaní, J., Paredes, R., et al.: Genotypic determination of HIV tropism—clinical and methodological recommendations to guide the therapeutic use of CCR5 antagonists. AIDS Rev. 12(3), 135–148 (2010)
Aiamkitsumrit, B., Dampier, W., Antell, G., et al.: Bioinformatic analysis of HIV-1 entry and pathogenesis. Curr. HIV Res. 12(2), 132–161 (2014)
Beerenwinkel, N., Daumer, M., Oette, M., et al.: Geno2pheno: estimating phenotypic drug resistance from HIV-1 genotypes. Nucleic Acids Res. 31(13), 3850–3855 (2003)
Soulie, C., Derache, A., Aime, C., et al.: Comparison of two genotypic algorithms to determine HIV-1 tropism. HIV Med. 9(1), 1–5 (2008)
Eisenberg, D., Weiss, R.M., Terwilliger, T.C.: The hydrophobic moment detects periodicity in protein. Proc. Natl. Acad. Sci. U.S.A. 81(1), 140–144 (1984)
Akaike, H.: A new look at the statistical model identification. IEEE Trans. Autom. Control 19(6), 716–723 (1974)
Skrabal, K., Low, A.J., Dong, W., et al.: Determining human immunodeficiency virus coreceptor use in a clinical setting: degree of correlation between two phenotypic assays and a bioinformatic model. J. Clin. Microbiol. 45(2), 279–284 (2007)
Riemenschneider, M., Cashin, K.Y., Budeus, B., et al.: Genotypic prediction of coreceptor tropism of HIV-1 subtypes A and C. Sci. Rep. 6(24883), 1–9 (2016)
He, H., Garcia, E.: Learning from imbalanced data. IEEE Trans. Knowl. Data Eng. 21(9), 1263–1284 (2009)
Cardozo, T., Kimura, T., Philpott, S., et al.: Structural basis for coreceptor selectivity by the HIV type 1 V3 loop. AIDS Res. Hum. Retroviruses 23(3), 415–426 (2007)
Isaka, Y., Sato, A., Miki, S., et al.: Small amino acid changes in the V3 loop of HIV type 2 determines the coreceptor usage for CXCR4 and CCR5. Virology 264(1), 237–243 (1999)
Lochel, H.F., Riemenschneider, M., Frishman, D., Heider, D.: Scotch: subtype A coreceptor tropism classification in HIV-1. Bioinformatics 1, 1–6 (2018)
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Barros, C., Raposo, L., Nobre, F. (2019). Logistic Regression Classifiers in the Analysis of HIV-1 Use of CCR5 and CXCR4 Coreceptors. In: Costa-Felix, R., Machado, J., Alvarenga, A. (eds) XXVI Brazilian Congress on Biomedical Engineering. IFMBE Proceedings, vol 70/1. Springer, Singapore. https://doi.org/10.1007/978-981-13-2119-1_103
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DOI: https://doi.org/10.1007/978-981-13-2119-1_103
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