Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIRaben-1 subtype B and non-subtype B receiving a salvage regimen
| Autor: | De Luca A., Flandre P., Dunn D., Zazzi M., Wensing A., Santoro M. M., Gunthard H. F., Wittkop L., Kordossis T., Garcia F., Castagna A., Cozzi-Lepri A., Churchill D., De Wit S., Brockmeyer N. H., Imaz A., Mussini C., Obel N., Perno C. F., Roca B., Reiss P., Schulter E., Torti C., van Sighem A., Zangerle R., Descamps D., Mocroft A., Kirk O., Sabin C., Casadi W., Casabona J., Miro J. M., Touloumi G., Garrido M., Teira R., Wit F., Warszawski J., Meyer L., Dabis F., Krause M. M., Ghosn J., Leport C., Prins M., Bucher H., Gibb D., Fatkenheuer G., del Amo J., Thorne C., Stephan C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., d'Arminio Monforte A., Prieto L., Conejo P. R., Soriano-Arandes A., Battegay M., Kouyos R., Tookey P., Konopnick D., Goetghebuer T., Sonnerborg A., Haerry D., de Wit S., Costagliola D., Raben D., Chene G., Ceccherini-Silberstein F., Gunthard H., Judd A., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Brandt R. S., Berenguer J., Bohlius J., Bouteloup V., Davies M. -A., Dorrucci M., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Schomaker M., Smit C., Sterne J., Thiebaut R., van der Valk M., Wyss N., Aubert V., Bernasconi E., Boni J., Burton-Jeangros C., Calmy A., Cavassini M., Dollenmaier G., Elzi L., Fehr J., Fellay J., Fux C. A., Gorgievski M., Hasse B., Hirsch H. H., Hoffmann M., Hosli I., Kahlert C., Kaiser L., Keiser O., Klimkait T., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Metzner K., Muller N., Nadal D., Nicca D., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schoni-Affolter F., Schmid P., Schupbach J., Speck R., Tarr P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S. |
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| Přispěvatelé: | De Luca, A, Flandre, P, Dunn, D, Zazzi, M, Wensing, A, Santoro, M, Gunthard, H, Wittkop, L, Kordossis, T, Garcia, F, Castagna, A, Cozzi-Lepri, A, Churchill, D, De Wit, S, Brockmeyer, N, Imaz, A, Mussini, C, Obel, N, Perno, C, Roca, B, Reiss, P, Schulter, E, Torti, C, van Sighem, A, Zangerle, R, Descamps, D, Mocroft, A, Kirk, O, Sabin, C, Casadi, W, Casabona, J, Miro, J, Touloumi, G, Garrido, M, Teira, R, Wit, F, Warszawski, J, Meyer, L, Dabis, F, Krause, M, Ghosn, J, Leport, C, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, del Amo, J, Thorne, C, Stephan, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, d'Arminio Monforte, A, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Haerry, D, de Wit, S, Costagliola, D, Raben, D, Chene, G, Ceccherini-Silberstein, F, Judd, A, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Davies, M, Dorrucci, M, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, van der Valk, M, Wyss, N, Aubert, V, Bernasconi, E, Boni, J, Burton-Jeangros, C, Calmy, A, Cavassini, M, Dollenmaier, G, Elzi, L, Fehr, J, Fellay, J, Fux, C, Gorgievski, M, Hasse, B, Hirsch, H, Hoffmann, M, Hosli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Metzner, K, Muller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rickenbach, M, Rudin, C, Schoni-Affolter, F, Schmid, P, Schupbach, J, Speck, R, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Weber, R, Yerly, S, University of Zurich, De Luca, Andrea, Santoro, Mm, Günthard, Hf, Brockmeyer, Nh, Perno, Cf, Schülter, E, on behalf of CHAIN and COHERE in, Eurocoord, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Infectious diseases, Medical Microbiology and Infection Prevention |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Male Enfuvirtide Genotyping Techniques HIV Infections 2726 Microbiology (medical) 10234 Clinic for Infectious Diseases 0302 clinical medicine HIV Protease Genotype 2736 Pharmacology (medical) Medicine HIV Infection Pharmacology (medical) 030212 general & internal medicine Non-U.S. Gov't Darunavir Aged 80 and over Microbial Sensitivity Test Medicine (all) Research Support Non-U.S. Gov't Proteolytic enzymes Middle Aged Settore MED/07 - Microbiologia e Microbiologia Clinica Prognosis Europe 3004 Pharmacology Treatment Outcome Infectious Diseases Mutation (genetic algorithm) Female Human medicine.drug Microbiology (medical) Adult medicine.medical_specialty Adolescent Pharmacology Prognosi Anti-HIV Agents 610 Medicine & health Microbial Sensitivity Tests Settore MED/17 - MALATTIE INFETTIVE Research Support Article 03 medical and health sciences Young Adult Internal medicine Linear regression Drug Resistance Viral Journal Article Humans Aged Receiver operating characteristic business.industry Anti-HIV Agent 2725 Infectious Diseases Raltegravir 030112 virology Virology HIV Darunavir Mutation HIV-1 genotypic Genotyping Technique business |
| Zdroj: | JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY r-FISABIO. Repositorio Institucional de Producción Científica instname Journal of Antimicrobial Chemotherapy, 71(5), 1352. Oxford University Press Journal of antimicrobial chemotherapy, 71(5), 1352-1360. Oxford University Press r-FISABIO: Repositorio Institucional de Producción Científica Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| ISSN: | 0305-7453 |
| Popis: | Objectives: The objective of this studywas to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. Methods: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large European databases. HIV-1 subtype B-infected patients were used as the derivation dataset and HIV- 1 non-B-infected patients were used as the validation dataset. The adjusted association of each mutation with week 8 HIV RNA change from baseline was analysed by linear regression. A prediction model was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). Results: TCEs were selected from 681 subtype B-infected and 199 non-B-infected adults. Accompanying drugs were NRTIs in 87%, NNRTIs in 27%and raltegravir ormaraviroc or enfuvirtide in 53%. The predictionmodel included weighted protease mutations, HIV RNA, CD4 and activity of accompanying drugs. The model's association with week 8 HIV RNA change in the subtype B (derivation) set was R2=0.47 [average squared error (ASE)=0.67, P>10-6]; in the non-B (validation) set, ASE was 0.91. Accuracy investigated by means of area under the receiver operating characteristic curves with a binary response (above the threshold value of HIV RNA reduction) showed that our finalmodel outperformed models with existing interpretation systems in both training and validation sets. Conclusions: A model with a new darunavir-weighted mutation score outperformed existing GISs in both B and non-B subtypes in predicting virological response to darunavir. |
| Databáze: | OpenAIRE |
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