Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.
Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial / Fabbiani, Massimiliano; Gagliardini, Roberta; Ciccarelli, Nicoletta; Roldan, Eugenia Quiros; Latini, Alessandra; D'Ettorre, Gabriella; Antinori, Andrea; Castagna, Antonella; Orofino, Giancarlo; Francisci, Daniela; Chinello, Pierangelo; Madeddu, Giordano; Grima, Pierfrancesco; Rusconi, Stefano; Del Pin, Barbara; Lombardi, FRANCESCA ELENA; D'Avino, Alessandro; Focà, Emanuele; Colafigli, Manuela; Cauda, Roberto; Di Giambenedetto, Simona; De Luca, Andrea; Mondi, A.; Borghetti, A.; Baldonero, E.; Belmonti, S.; Lamonica, S.; Sidella, L.; Tamburrini, E.; Visconti, E.; Giacometti, A.; Barchiesi, F.; Castelli, P.; Cirioni, O.; Mazzocato, S.; DI PIETRO, Marinella; Blanc, P.; Degli Esposti, A.; Mariabelli, E.; Marini, Stefano; Poggi, A.; Quiros Roldan, E.; Amadasi, S.; Apostoli, A.; Biasi, L.; Bonito, A.; Brianese, N.; Compostella, S.; Ferraresi, A.; Motta, D.; Mughini, M. T.; Celesia, B. M.; Gussio, M.; Sofia, S.; Tana, M.; Tundo, P.; Viscoli, C.; De Hoffer, L.; Di Biagio, A.; Grignolo, S.; Parisini, A.; Schenone, E.; Taramasso, L.; Manconi, P. E.; Boccone, A.; Ortu, F.; Piano, P.; Serusi, L.; Puoti, M.; Moioli, M. C.; Rossotti, R.; Travi, G.; Ventura, Fiammetta; Galli, M.; Di Nardo Stuppino, S.; Di Cristo, V.; Giacomelli, Andrea; Vimercati, V.; Viale, P.; Gori, A.; Rizzardini, G.; Capetti, A.; Carenzi, L.; Mazza, F.; Meraviglia, P.; DE ROSA, Stefano; Zucchi, Paolo; Mineo, Martina; Giuliani, M.; Pacifici, A.; Pimpinelli, F.; Solivetti, F.; Stivali, F.; Angelici, Francesca; Bellagamba, Roberta; Delle Rose, D.; Fezza, R.; Libertone, R.; Mosti, S.; Narciso, P.; Nicastri, E.; Ottou, S.; Tomassi, C.; Vlassi, C.; Zaccarelli, M.; Zoppè, F.; Vullo, V.; Altavilla, F.; Ceccarelli, Gabriele; Fantauzzi, A.; Gebremeskel, S.; Lo Menzo, S.; Mezzaroma, I.; Tierno, F.; Petrosillo, N.; Boumis, E.; Cicalini, S.; Grilli, E.; Musso, M.; Stella, C.; Mura, M. S.; Bagella, P.; Mannazzu, M.; Soddu, V.; Caramello, P.; Carcieri, C.; Carosella, S.; Farenga, M.; Scotton, P. G.; Rossi, M. C.; Concia, E.; Corsini, F.; Gricolo, C.; Lanzafame, M.; Lattuada, E.; Leonardi, S.; Rigo, F.; Lazzarin, A.; Bigoloni, A.; Carini, E.; Nozza, S.; Spagnuolo, V.; Belfiori, B.; Malincarne, L.; Schiaroli, E.; Sfara, C.; Tosti, A.; Sacchini, D.; Ruggieri, A.; Valdatta, C.. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - STAMPA. - 73:7(2018), pp. 1955-1964. [10.1093/jac/dky123]
Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial
Giacometti, A.;Barchiesi, F.;Castelli, P.;Cirioni, O.;Mazzocato, S.;VENTURA, FIAMMETTA;Galli, M.;GIACOMELLI, ANDREA;
2018-01-01
Abstract
Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
