Three-class-resistant human immunodeficiency virus type 1 variant in a drug-naive heterosexual couple

Combination antiretroviral treatment was initiated in a heterosexual couple newly diagnosed with human immunodeficiency virus type 1 infection. Multiple genotypic drug resistance testing following early rebound of viral load revealed that the same three-class-resistant human immunodeficiency virus type 1 strain had been present in both patients since before initiation of treatment

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)

none149noBackground: 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.mixedDi 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.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

Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial

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/mm 3 . 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