{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:25:35Z","timestamp":1777440335413,"version":"3.51.4"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":3015,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Optimizing HIV therapies is crucial since the virus rapidly develops mutations to evade drug pressure. Recent studies have shown that genotypic information might not be sufficient for the design of therapies and that other clinical and demographical factors may play a role in therapy failure. This study is designed to assess the improvement in prediction achieved when such information is taken into account. We use these factors to generate a prediction engine using a variety of machine learning methods and to determine which clinical conditions are most misleading in terms of predicting the outcome of a therapy.<\/jats:p>\n               <jats:p>Results: Three different machine learning techniques were used: generative\u2013discriminative method, regression with derived evolutionary features, and regression with a mixture of effects. All three methods had similar performances with an area under the receiver operating characteristic curve (AUC) of 0.77. A set of three similar engines limited to genotypic information only achieved an AUC of 0.75. A straightforward combination of the three engines consistently improves the prediction, with significantly better prediction when the full set of features is employed. The combined engine improves on predictions obtained from an online state-of-the-art resistance interpretation system. Moreover, engines tend to disagree more on the outcome of failure therapies than regarding successful ones. Careful analysis of the differences between the engines revealed those mutations and drugs most closely associated with uncertainty of the therapy outcome.<\/jats:p>\n               <jats:p>Availability: The combined prediction engine will be available from July 2008, see http:\/\/engine.euresist.org<\/jats:p>\n               <jats:p>Contact: \u00a0rosen@il.ibm.com<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn141","type":"journal-article","created":{"date-parts":[[2008,6,27]],"date-time":"2008-06-27T07:43:13Z","timestamp":1214552593000},"page":"i399-i406","source":"Crossref","is-referenced-by-count":43,"title":["Selecting anti-HIV therapies based on a variety of genomic and clinical factors"],"prefix":"10.1093","volume":"24","author":[{"given":"Michal","family":"Rosen-Zvi","sequence":"first","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Altmann","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattia","family":"Prosperi","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehud","family":"Aharoni","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hani","family":"Neuvirth","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"S\u00f6nnerborg","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugen","family":"Sch\u00fclter","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Struck","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yardena","family":"Peres","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Incardona","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Kaiser","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Zazzi","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Lengauer","sequence":"additional","affiliation":[{"name":"1 Machine learning group, IBM Research Laboratory in Haifa, Israel, 2The Computational Biology and Applied Algorithmics Department, Max Planck Institute for Informatics, Saarbr\u00fccken, Germany, 3Computer Science and Automation Department, University of Rome TRE, Italy, 4Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Sweden, 5Institute of Virology, University of Cologne, Cologne, Germany, 6Retrovirology Laboratory, CRP-Sant\u00e9, Luxembourg, 7Health care and Life sciences group, IBM Research Laboratory in Haifa, Israel, 8Informa srl, Rome, Italy and 9Department of Molecular Biology, University of Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,7,1]]},"reference":[{"key":"2023020210400541300_B1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","article-title":"A new look at the statistical model identification","volume":"19","author":"Akaike","year":"1974","journal-title":"IEEE Trans. Automat. Contr"},{"key":"2023020210400541300_B2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1177\/135965350701200202","article-title":"Improved prediction of response to antiretroviral combination therapy using the genetic barrier to drug resistance","volume":"12","author":"Altmann","year":"2007","journal-title":"Antivir. ther"},{"key":"2023020210400541300_B3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol"},{"key":"2023020210400541300_B4","doi-asserted-by":"crossref","first-page":"3850","DOI":"10.1093\/nar\/gkg575","article-title":"Geno2pheno: Estimating phenotypic drug resistance from HIV-1 genotypes","volume":"31","author":"Beerenwinkel","year":"2003","journal-title":"Nucleic Acids Res."},{"issue":"Suppl. 1","key":"2023020210400541300_B5","doi-asserted-by":"crossref","first-page":"s14","DOI":"10.1097\/QAI.0b013e3180600766","article-title":"The role of adherence to antiretroviral therapy in the management of HIV Infection","volume":"45","author":"Conway","year":"2007","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr"},{"key":"2023020210400541300_B6","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1086\/502976","article-title":"Frequency and treatment-related predictors of thymidine-analogue mutation patterns in HIV-1 isolates after unsuccessful antiretroviral therapy","volume":"193","author":"De Luca","year":"2006","journal-title":"J. Infect. Dis."},{"key":"2023020210400541300_B7","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1177\/135965350300800605","article-title":"Review: nucleoside and nucleotide analogue reverse transcriptase inhibitors: a clinical review of antiretroviral resistance","volume":"8","author":"Gallant","year":"2003","journal-title":"Antivir. Ther"},{"key":"2023020210400541300_B8","article-title":"Correlation-based Feature Selection for Machine Learning","volume-title":"Ph.D Dissertation","author":"Hall","year":"1998"},{"key":"2023020210400541300_B9","first-page":"54","article-title":"Application of ridge analysis to regression problems","volume":"58","author":"Hoerl","year":"1962","journal-title":"Chem. Eng. Progress"},{"key":"2023020210400541300_B10","first-page":"119","article-title":"Update of the drug resistance mutations in HIV-1: 2007","volume":"15","author":"Johnson","year":"2007","journal-title":"Top HIV Med."},{"key":"2023020210400541300_B11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/135965350701200112","article-title":"The development of artificial neural networks to predict virological response to combination HIV therapy","volume":"12","author":"Larder","year":"2007","journal-title":"Antivir. ther"},{"key":"2023020210400541300_B12","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2307\/2347628","article-title":"Ridge estimators in logistic regression","volume":"41","author":"Le Cessie","year":"1992","journal-title":"Appl. Stat"},{"key":"2023020210400541300_B13","article-title":"Inference for the generalization error","volume":"12","author":"Nadeau","year":"2000","journal-title":"Adv. Neural Inf. Process. Syst"},{"key":"2023020210400541300_B14","volume-title":"Probabilistic reasoning in intelligent systems: networks of plausible inference","author":"Pearl","year":"1988"},{"key":"2023020210400541300_B15","first-page":"1","article-title":"Early factors in successful anti-HIV treatment","volume":"2","author":"Piliero","year":"2003","journal-title":"J. Int. Assoc. Physicians in AIDS Care (JIAPAC)"},{"key":"2023020210400541300_B16","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/nar\/gkg100","article-title":"Human immunodeficiency virus reverse transcriptase and protease sequence database","volume":"31","author":"Rhee","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"2023020210400541300_B17","doi-asserted-by":"crossref","DOI":"10.1007\/11799511_16","article-title":"Arevir: a secure platfrom for designing personalized antiretroviral therapies against HIV. In","volume-title":"Third International Workshop on Data Integration in the Life Sciences (DILS 2006)","author":"Roomp","year":"2006"},{"key":"2023020210400541300_B18","article-title":"Viral reservoirs and ongoing virus replication in patients on HAART: implications for clinical management","author":"Siliciano","year":"2001","journal-title":"Conf. Retrovir. Oppor. Infect"},{"key":"2023020210400541300_B19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jviromet.2007.05.009","article-title":"Prediction of HIV-1 drug susceptibility phenotype from the viral genotype using linear regression modeling","volume":"145","author":"Vermeiren","year":"2007","journal-title":"J. Virol. Methods"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/13\/i399\/49053197\/bioinformatics_24_13_i399.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/13\/i399\/49053197\/bioinformatics_24_13_i399.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T12:23:49Z","timestamp":1675340629000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/13\/i399\/226470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,1]]},"references-count":19,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2008,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn141","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,7,1]]},"published":{"date-parts":[[2008,7,1]]}}}