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.

Original languageEnglish
Pages (from-to)1955-1964
Number of pages10
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number7
DOIs
Publication statusPublished - Jul 1 2018

Fingerprint

Ritonavir
Lamivudine
HIV
Therapeutics
Bone Density
Kidney
Safety
Hyperbilirubinemia
Atazanavir Sulfate
Hypertriglyceridemia
Treatment Failure
Spine
RNA
DNA

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients : 96 week outcomes of a randomized trial. / on behalf of the AtLaS-M Study Group.

In: Journal of Antimicrobial Chemotherapy, Vol. 73, No. 7, 01.07.2018, p. 1955-1964.

Research output: Contribution to journalArticle

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title = "Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial",
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.",
author = "{on behalf of the AtLaS-M Study Group} and Massimiliano Fabbiani and Roberta Gagliardini and Nicoletta Ciccarelli and Roldan, {Eugenia Quiros} and A. Latini and Gabriella d'Ettorre and A. Antinori and A. Castagna and Giancarlo Orofino and Daniela Francisci and P. Chinello and F. Lombardi and M. Colafigli and A. Mondi and F. Lombardi and {De Luca}, A. and A. Poggi and C. Viscoli and M. Galli and A. Gori and A. Latini and M. Colafigli and M. Giuliani and A. Pacifici and F. Pimpinelli and F. Solivetti and F. Stivali and A. Antinori and R. Bellagamba and R. Libertone and S. Mosti and P. Narciso and E. Nicastri and S. Ottou and M. Zaccarelli and N. Petrosillo and N. Petrosillo and P. Chinello and E. Boumis and S. Cicalini and E. Grilli and M. Musso and Mura, {M. S.} and Rossi, {M. C.} and S. Leonardi and A. Lazzarin and A. Castagna and S. Nozza and V. Spagnuolo and A. Ruggieri",
year = "2018",
month = "7",
day = "1",
doi = "10.1093/jac/dky123",
language = "English",
volume = "73",
pages = "1955--1964",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
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TY - JOUR

T1 - Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients

T2 - 96 week outcomes of a randomized trial

AU - on behalf of the AtLaS-M Study Group

AU - Fabbiani, Massimiliano

AU - Gagliardini, Roberta

AU - Ciccarelli, Nicoletta

AU - Roldan, Eugenia Quiros

AU - Latini, A.

AU - d'Ettorre, Gabriella

AU - Antinori, A.

AU - Castagna, A.

AU - Orofino, Giancarlo

AU - Francisci, Daniela

AU - Chinello, P.

AU - Lombardi, F.

AU - Colafigli, M.

AU - Mondi, A.

AU - Lombardi, F.

AU - De Luca, A.

AU - Poggi, A.

AU - Viscoli, C.

AU - Galli, M.

AU - Gori, A.

AU - Latini, A.

AU - Colafigli, M.

AU - Giuliani, M.

AU - Pacifici, A.

AU - Pimpinelli, F.

AU - Solivetti, F.

AU - Stivali, F.

AU - Antinori, A.

AU - Bellagamba, R.

AU - Libertone, R.

AU - Mosti, S.

AU - Narciso, P.

AU - Nicastri, E.

AU - Ottou, S.

AU - Zaccarelli, M.

AU - Petrosillo, N.

AU - Petrosillo, N.

AU - Chinello, P.

AU - Boumis, E.

AU - Cicalini, S.

AU - Grilli, E.

AU - Musso, M.

AU - Mura, M. S.

AU - Rossi, M. C.

AU - Leonardi, S.

AU - Lazzarin, A.

AU - Castagna, A.

AU - Nozza, S.

AU - Spagnuolo, V.

AU - Ruggieri, A.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

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U2 - 10.1093/jac/dky123

DO - 10.1093/jac/dky123

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VL - 73

SP - 1955

EP - 1964

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 7

ER -