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.

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 / G.A. Meini, B.B. Rossetti, C.B. Bianco, F.C. Ceccherini Silberstein, S.D. Di Giambenedetto, L.E. Sighinolfi, L.F. Monno, A.G. Castagna, G.H. Rozera, A. D'arminio Monforte, M.A. Zazzi, A.B. De Luca, M.A. Moroni, O.A. Armignacco, R.A. Iardino, G.A. Ippolito, C.F.A. Perno, F.A. Von Schloesser, A.A. Cozzi Lepri, E.A. Girardi, C.A. Balotta, M.A. Borderi, M.R.A. Capobianchi, P.A. Cinque, A.A. Di Biagio, N.A. Gianotti, G.A. Guaraldi, M.A. Lichtner, S.A. Marcotullio, S.A. Rusconi, T.A. Formenti, L.A. Galli, P.A. Lorenzini, A.J. Giacometti, A.J. Costantini, G.K. Angarano, C.K. Santoro, F.L. Maggiolo, C.L. Suardi, P.M. Viale, E.M. Vanino, G.M. Verucchi, F.N. Castelli, E.N. Quiros Roldan, C.N. Minardi, T.O. Quirino, C.O. Abeli, P.E.P. Manconi, P.P. Piano, J.Q. Vecchiet, K.Q. Falasca, D.R. Segala, F.S. Mazzotta, S.S. Lo Caputo, G.T. Cassola, G.T. Viscoli, A.T. Alessandrini, R.T. Piscopo, G.T. Mazzarello, C.U. Mastroianni, V.U. Belvisi, P.V. Bonfanti, I.V. Caramma, A.P.W. Castelli, M.X. Galli, A.X. Lazzarin, G.X. Rizzardini, M.X. Puoti, A.L.X. Ridolfo, R.X. Piolini, S. Salpietro, L. Carenzi, M.C.X. Moioli, P. Cicconi, G. Marchetti, C.Y. Mussini, C.Y. Puzzolante, A.Z. Gori, G.Z. Lapadula, N.A. Abrescia, A.A. Chirianni, M.G.A. Guida, M.A. Gargiulo, F.A. Baldelli, D.A. Francisci, G.A. Parruti, T.A. Ursini, G.A. Magnani, M.A.A. Ursitti, R.A. Cauda, M.A. Andreoni, A.A. Antinori, V.A. Vullo, A.A. Cingolani, A.A. D'Avino, A.A. Ammassari, L.A. Gallo, E.A. Nicastri, R.A. Acinapura, M.A. Capozzi, R.A. Libertone, G.A. Tebano, A.A. Cattelan, M.S.A. Mura, G.A. Madeddu, P.A. Caramello, G.A. Di Perri, G.C.A. Orofino, S.A. Bonora, M.A. Sciandra, G.A. Pellizzer, V.A. Manfrin. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 69:3(2014 Mar), pp. dkt426.735-dkt426.741.

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

A. D'arminio Monforte;S.A. Rusconi;G. Marchetti;A.Z. Gori;
2014

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.
HIV type 1 ; V3 ; genotype interpretation ; gp120 ; virological response ; genotypic prediction ; infected patients ; treated patients ; maraviroc ; plasma ; management ; evolution ; V3-loop ; samples
Settore MED/17 - Malattie Infettive
mar-2014
Article (author)
File in questo prodotto:
File Dimensione Formato  
735.full.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 244.35 kB
Formato Adobe PDF
244.35 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/234982
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 13
social impact