Evolution of HIV-1 tropism at quasispecies level after 5 years of combination antiretroviral therapy in patients always suppressed or experiencing episodes of virological failure
التفاصيل البيبلوغرافية
العنوان:
Evolution of HIV-1 tropism at quasispecies level after 5 years of combination antiretroviral therapy in patients always suppressed or experiencing episodes of virological failure
Rozera, G, Abbate, I, Giombini, E, Castagna, A, De Luca, A, Ceccherini Silberstein, F, Cozzi Lepri, A, Cassola, G, Torti, C, d'Arminio Monforte, A, Ippolito, G, Capobianchi, M, Gori, A, Rozera G, Abbate I, Giombini E, Castagna A, De Luca A, Ceccherini-Silberstein F, Cozzi Lepri A, Cassola G, Torti C, d'Arminio Monforte A, Ippolito G, Capobianchi MR, ICONA Foundation Group […, Moroni M, Andreoni M, Angarano G, Antinori A, Castelli F, Cauda R, Di Perri G, Galli M, Iardino R, Lazzarin A, Perno C, von Schloesser F, Girardi E, Lo Caputo S, Mussini C, Puoti M, Ammassari A, Balotta C, Bonfanti P, Bonora S, Borderi M, Cingolani A, Cinque P, Gianotti N, Gori A, Guaraldi G, Lapadula G, Lichtner M, Madeddu G, Maggiolo F, Marchetti G, Marcotullio S, Monno L, Quiros Roldan E, Rusconi S, Cicconi P, Fanti I, Formenti T, Galli L, Lorenzini P, Carletti F, Carrara S, Castrogiovanni A, Di Caro A, Petrone F, Prota G, Quartu S, Giacometti A, Costantini A, Mazzoccato S, Santoro C, Suardi C, Viale P, Vanino E, Verucchi G, Minardi C, Quirino T, Abeli C, Manconi P, Piano P, Vecchiet J, Falasca K, Sighinolfi L, Segala D, Mazzotta F, Viscoli C, Alessandrini A, Piscopo R, Mazzarello G, Mastroianni C, Belvisi V, Caramma I, Chiodera A, Castelli A, Rizzardini G, Ridolfo A, Piolini R, Salpietro S, Carenzi L, Moioli M, Tincati C, Puzzolante C, Abrescia N, Chirianni A, Guida M, Gargiulo M, Baldelli F, Francisci D, Parruti G, Ursini T, Magnani G, Ursitti M, Vullo V, d'Avino A, Gallo L, Nicastri E, Acinapura R, Capozzi M, Libertone R, Tebano G, Cattelan A, Sasset L, Mura M, Rossetti B, Caramello P, Orofino G, Sciandra M, Bassetti M, Londero A, Pellizzer G, Manfrin V, …], Rozera, Gabriella, Abbate, Isabella, Giombini, Emanuela, ICONA Fdn, Grp, Castagna, Antonella
Received 27 February 2014; returned 15 April 2014; revised 29 May 2014; accepted 12 June 2014Objectives:Tropism evolution of HIV-1 quasispecies was analysed by ultra-deep pyrosequencing (UDPS) inpatients on first-line combination antiretroviral therapy (cART) always suppressed or experiencing virologicalfailure episodes.Methods:Among ICONA patients, two groups of 20 patients on cARTfor ≥5 years, matched for baseline viraemiaand therapy duration, were analysed [Group I, patients always suppressed; and Group II, patients experiencingepisode(s) of virological failure]. Viral tropism was assessed by V3 UDPS on plasma RNA before therapy (T0) andon peripheral blood mononuclearcell proviral DNA before–after therapy (T0-T1), using geno2pheno false positiverate (FPR) (threshold for X4: 5.75). For each sample, quasispecies tropism was assigned according to X4 variantfrequency: R5, ,0.3% X4; minority X4, 0.3%–19.9% X4; and X4, ≥20% X4. An R5–X4 switch was defined as achange from R5/minority X4 in plasma/proviral genomes at T0 to X4 in provirus at T1.Results: At baseline, mean FPR and %X4 of viral RNA were positively correlated with those of proviral DNA. Aftertherapy, proviral DNA load significantly decreased in Group I; mean FPR of proviral quasispecies significantlydecreased and %X4 increased in Group II. An R5–X4 switch was observed in five patients (two in Group I andthree in Group II), all harbouring minority X4 variants at T0.Conclusions:UDPS analysis revealsthat the tropism switch isnot an ‘on–off’ phenomenon, but may result fromaprofound re-shaping of viral quasispecies, even under suppressive cART. However, episodes of virological failureseem to prevent reduction of proviral DNA and to accelerate viral evolution, as suggested by decreased FPR andincreased %X4 at T1 in Group II patients.Keywords: cART, HIV quasispecies, co-receptor usage, ultra-deep pyrosequencing, tropism switch
