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.

Di Giambenedetto, S., Fabbiani, M., Quiros Roldan, E., Latini, A., D'Ettorre, G., Antinori, A., et al. (2017). 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). JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 72(4), 1163-1171 [10.1093/jac/dkw557].

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)

Puoti M.;Gori A.;
2017

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.
Articolo in rivista - Articolo scientifico
ART HIV;
English
1163
1171
9
Di Giambenedetto, S., Fabbiani, M., Quiros Roldan, E., Latini, A., D'Ettorre, G., Antinori, A., et al. (2017). 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). JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 72(4), 1163-1171 [10.1093/jac/dkw557].
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; Foca, 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; Celesia, B; 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; Boccone, A; Ortu, F; Piano, P; Serusi, L; Puoti, M; Moioli, M; 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; Zoppe, 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; Bagella, P; Mannazzu, M; Soddu, V; Caramello, P; Carcieri, C; Carosella, S; Farenga, M; Scotton, P; Rossi, M; 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
File in questo prodotto:
Non ci sono file associati a questo prodotto.

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/10281/352577
Citazioni
  • Scopus 71
  • ???jsp.display-item.citation.isi??? 66
Social impact