Treatment simplification to atazanavir/ritonavir+lamivudine versus maintenance of atazanavir/ritonavir+two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M)

Di Giambenedetto, S.; Fabbiani, M.; Quiros Roldan, E.; Latini, A.; D'Ettorre, G.; Antinori, A.; Castagna, A.; Orofino, G.; Francisci, D.; Chinello, P.; Madeddu, G.; Grima, P.; Rusconi, S.; Di Pietro, M.; Mondi, A.; Ciccarelli, N.; Borghetti, A.; Focà, E.; Colafigli, M.; De Luca, A.; Cauda, R.; Baldonero, E.; Belmonti, S.; D'Avino, A.; Gagliardini, R.; Lamonica, S.; Lombardi, F.; Sidella, L.; Tamburrini, E.; Visconti, E.; Giacometti, A.; Barchiesi, F.; Castelli, P.; Cirioni, O.; Mazzocato, S.; Blanc, P.; Degli Esposti, A.; Del Pin, B.; Mariabelli, E.; Marini, S.; Poggi, A.; 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, F.; Galli, M.; Di Nardo Stuppino, S.; Di Cristo, V.; Giacomelli, A.; Vimercati, V.; Viale, P.; Gori, A.; Rizzardini, G.; Capetti, A.; Carenzi, L.; Mazza, F.; Meraviglia, P.; Rosa, S.; Zucchi, P.; Mineo, M.; Giuliani, M.; Pacifici, A.; Pimpinelli, F.; Solivetti, F.; Stivali, F.; Angelici, F.; Bellagamba, R.; 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, G.; 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.

doi:10.1093/jac/dkw557

Background: Combination ART (cART)-related toxicities and costs have prompted the need for treatment simplification. The ATLAS-M trial explored 48 week non-inferior efficacy of simplification to atazanavir/ritonavir + lamivudine versus maintaining three-drug atazanavir/ritonavir-based cART in virologically suppressed patients. Methods: We performed an open-label, multicentre, randomized, non-inferiority study, enrolling HIV-infected adults on atazanavir/ritonavir+two NRTIs, with stable HIV-RNA <50 copies/mL and CD4+>200 cells/mm3. Main exclusion criteria were hepatitis B virus coinfection, past virological failure on or resistance to study drugs, recent AIDS and pregnancy. Patients were randomly assigned 1:1 to either switch to 300mg of atazanavir/ 100mg of ritonavir once daily and 300mg of lamivudine once daily (atazanavir/ritonavir+lamivudine arm) or to continue the previous regimen (atazanavir/ritonavir+two NRTIs arm). The primary study outcome was the maintenance of HIV-RNA <50 copies/mL at week 48 of the ITT-exposed (ITT-e) analysis with switch"failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, number NCT01599364. Results: Between July 2011 and June 2014, 266 patients were randomized (133 to each arm). After 48 weeks, the primary study outcome was met by 119 of 133 patients (89.5%) in the atazanavir/ritonavir+lamivudine arm and 106 of 133 patients (79.7%) in the atazanavir/ritonavir+two NRTIs arm [difference atazanavir/ritonavir+ lamivudine versus atazanavir/ritonavir+two NRTIs arm: +9.8% (95% CI+1.2 to+18.4)], demonstrating non-inferiority and superior efficacy of the atazanavir/ritonavir+lamivudine arm. Virological failure occurred in two (1.5%) patients in the atazanavir/ritonavir+lamivudine arm and six (4.5%) patients in the atazanavir/ritonavir+ two NRTIs arm, without resistance selection. A similar proportion of adverse events occurred in both arms. Conclusions: Treatment simplification to atazanavir/ritonavir+lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir+two NRTIs in virologically suppressed patients.

Treatment simplification to atazanavir/ritonavir+lamivudine versus maintenance of atazanavir/ritonavir+two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M)

Di Giambenedetto, S.;Fabbiani, M.;Quiros Roldan, E.;Latini, A.;D'Ettorre, G.;Antinori, A.;Castagna, A.;Orofino, G.;Francisci, D.;Chinello, P.;Madeddu, G.;Grima, P.;Rusconi, S.;Di Pietro, M.;Mondi, A.;Ciccarelli, N.;Borghetti, A.;Focà, E.;Colafigli, M.;De Luca, A.;Cauda, R.;Baldonero, E.;Belmonti, S.;D'Avino, A.;Gagliardini, R.;Lamonica, S.;Lombardi, F.;Sidella, L.;Tamburrini, E.;Visconti, E.;Giacometti, A.;Barchiesi, F.;Castelli, P.;Cirioni, O.;Mazzocato, S.;Blanc, P.;Degli Esposti, A.;Del Pin, B.;Mariabelli, E.;Marini, S.;Poggi, A.;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, F.;Galli, M.;Di Nardo Stuppino, S.;Di Cristo, V.;Giacomelli, A.;Vimercati, V.;Viale, P.;Gori, A.;Rizzardini, G.;Capetti, A.;Carenzi, L.;Mazza, F.;Meraviglia, P.;Rosa, S.;Zucchi, P.;Mineo, M.;Giuliani, M.;Pacifici, A.;Pimpinelli, F.;Solivetti, F.;Stivali, F.;Angelici, F.;Bellagamba, R.;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, G.;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.

2017-01-01

Abstract

Background: Combination ART (cART)-related toxicities and costs have prompted the need for treatment simplification. The ATLAS-M trial explored 48 week non-inferior efficacy of simplification to atazanavir/ritonavir + lamivudine versus maintaining three-drug atazanavir/ritonavir-based cART in virologically suppressed patients. Methods: We performed an open-label, multicentre, randomized, non-inferiority study, enrolling HIV-infected adults on atazanavir/ritonavir+two NRTIs, with stable HIV-RNA <50 copies/mL and CD4+>200 cells/mm3. Main exclusion criteria were hepatitis B virus coinfection, past virological failure on or resistance to study drugs, recent AIDS and pregnancy. Patients were randomly assigned 1:1 to either switch to 300mg of atazanavir/ 100mg of ritonavir once daily and 300mg of lamivudine once daily (atazanavir/ritonavir+lamivudine arm) or to continue the previous regimen (atazanavir/ritonavir+two NRTIs arm). The primary study outcome was the maintenance of HIV-RNA <50 copies/mL at week 48 of the ITT-exposed (ITT-e) analysis with switch"failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, number NCT01599364. Results: Between July 2011 and June 2014, 266 patients were randomized (133 to each arm). After 48 weeks, the primary study outcome was met by 119 of 133 patients (89.5%) in the atazanavir/ritonavir+lamivudine arm and 106 of 133 patients (79.7%) in the atazanavir/ritonavir+two NRTIs arm [difference atazanavir/ritonavir+ lamivudine versus atazanavir/ritonavir+two NRTIs arm: +9.8% (95% CI+1.2 to+18.4)], demonstrating non-inferiority and superior efficacy of the atazanavir/ritonavir+lamivudine arm. Virological failure occurred in two (1.5%) patients in the atazanavir/ritonavir+lamivudine arm and six (4.5%) patients in the atazanavir/ritonavir+ two NRTIs arm, without resistance selection. A similar proportion of adverse events occurred in both arms. Conclusions: Treatment simplification to atazanavir/ritonavir+lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir+two NRTIs in virologically suppressed patients.