1. Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy
- Author
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Meini, G., Rossetti, B., Bianco, C., Ceccherini-Silberstein, F., Di Giambenedetto, S., Sighinolfi, L., Monno, L., Castagna, A., Rozera, G., D'Arminio Monforte, A., Zazzi, M., De Luca, A., Moroni, M., Angarano, G., Antinori, A., Armignacco, O., d'Arminio Monforte, A., Castelli, F., Cauda, R., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, C. F., von Schloesser, F., Viale, P., Cozzi-Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Andreoni, M., Ammassari, A., Balotta, C., Bonfanti, P., Bonora, S., Borderi, M., Capobianchi, M. R., Cingolani, A., Cinque, P., Di Biagio, A., Gianotti, N., Gori, A., Guaraldi, G., Lapadula, G., Lichtner, M., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Quiros Roldan, E., Rusconi, S., Cicconi, P., Fanti, I., Formenti, T., Galli, L., Lorenzini, P., Giacometti, A., Costantini, A., Santoro, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Segala, D., Mazzotta, F., Cassola, G., Viscoli, G., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Puzzolante, C., Abrescia, N., Chirianni, A., Guida, M. G., Gargiulo, M., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., Vullo, V., d'Avino, A., Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Tebano, G., Cattelan, A., Mura, M. S., Caramello, P., Orofino, G. C., Sciandra, M., Pellizzer, G., Manfrin, V., Meini, Genny, Rossetti, Barbara, Bianco, Claudia, ICONA Fdn, Grp, Castagna, Antonella, Meini, G, Rossetti, B, Bianco, C, Ceccherini Silberstein, F, Di Giambenedetto, S, Sighinolfi, L, Monno, L, Castagna, A, Rozera, G, D'arminio Monforte, A, Zazzi, M, De Luca, A, Moroni, M, Armignacco, O, Iardino, R, Ippolito, G, Perno, C, Von Schloesser, F, Cozzi Lepri, A, Girardi, E, Balotta, C, Borderi, M, Capobianchi, M, Cinque, P, Di Biagio, A, Gianotti, N, Guaraldi, G, Lichtner, M, Marcotullio, S, Rusconi, S, Formenti, T, Galli, L, Lorenzini, P, Giacometti, A, Costantini, A, Angarano, G, Santoro, C, Maggiolo, F, Suardi, C, Viale, P, Vanino, E, Verucchi, G, Castelli, F, Quiros Roldan, E, Minardi, C, Quirino, T, Abeli, C, Manconi, P, Piano, P, Vecchiet, J, Falasca, K, Segala, D, Mazzotta, F, Lo Caputo, S, Cassola, G, Viscoli, G, Alessandrini, A, Piscopo, R, Mazzarello, G, Mastroianni, C, Belvisi, V, Bonfanti, P, Caramma, I, Castelli, A, Galli, M, Lazzarin, A, Rizzardini, G, Puoti, M, Ridolfo, A, Piolini, R, Salpietro, S, Carenzi, L, Moioli, M, Cicconi, P, Marchetti, G, Mussini, C, Puzzolante, C, Gori, A, Lapadula, G, Abrescia, N, Chirianni, A, Guida, M, Gargiulo, M, Baldelli, F, Francisci, D, Parruti, G, Ursini, T, Magnani, G, Ursitti, M, Cauda, R, Andreoni, M, Antinori, A, Vullo, V, Cingolani, A, D'Avino, A, Ammassari, A, Gallo, L, Nicastri, E, Acinapura, R, Capozzi, M, Libertone, R, Tebano, G, Cattelan, A, Mura, M, Madeddu, G, Caramello, P, Di Perri, G, Orofino, G, Bonora, S, Sciandra, M, Pellizzer, G, and Manfrin, V
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Male ,viruses ,Salvage therapy ,HIV Infections ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,Genotype interpretation ,gp120 ,HIV type 1 ,V3 ,Adult ,Anti-Retroviral Agents ,Antiretroviral Therapy, Highly Active ,DNA, Viral ,Female ,Genotype ,HIV-1 ,Humans ,RNA, Viral ,Sequence Analysis, DNA ,Viral Tropism ,Pharmacology ,Pharmacology (medical) ,Infectious Diseases ,Medicine (all) ,HIV Infection ,Viral ,030212 general & internal medicine ,Original Research ,0303 health sciences ,tropism ,virus diseases ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,3. Good health ,genotype interpretation ,Sequence Analysis ,Human ,Microbiology (medical) ,antiretroviral therapy ,Antiretroviral Therapy ,Viremia ,Infectious Disease ,CCR5 receptor antagonist ,Biology ,HIV infection ,Settore MED/17 - MALATTIE INFETTIVE ,NO ,03 medical and health sciences ,medicine ,Highly Active ,Tropism ,Maraviroc ,030306 microbiology ,RNA ,DNA ,medicine.disease ,Virology ,chemistry ,Immunology ,Tissue tropism ,Anti-Retroviral Agent ,Cohort Studie - Abstract
Objectives: Maraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment. Methods: HIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated. Results: Coreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing. Conclusions: HIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
- Published
- 2013
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