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

被引：73

作者：

Di Giambenedetto, Simona ^{[1
]}

Fabbiani, Massimiliano ^{[1
]}

Roldan, Eugenia Quiros ^{[2
]}

Latini, Alessandra ^{[3
]}

D'Ettorre, Gabriella ^{[4
]}

Antinori, Andrea ^{[5
]}

Castagna, Antonella ^{[6
]}

Orofino, Giancarlo ^{[7
]}

Francisci, Daniela ^{[8
]}

Chinello, Pierangelo ^{[9
]}

Madeddu, Giordano ^{[10
]}

Grima, Pierfrancesco ^{[11
]}

Rusconi, Stefano ^{[12
]}

Di Pietro, Massimo ^{[13
]}

Mondi, Annalisa ^{[1
]}

Ciccarelli, Nicoletta ^{[1
]}

Borghetti, Alberto ^{[1
]}

Foca, Emanuele ^{[2
]}

Colafigli, Manuela ^{[3
]}

De Luca, Andrea ^{[14
,15
]}

Cauda, Roberto ^{[1
]}

机构：

[1] Univ Cattolica Sacro Cuore, Inst Clin Infect Dis, Rome, Italy

[2] Univ Brescia, Univ Div Infect & Trop Dis, Brescia, Italy

[3] IFO S Gallicano Inst IRCCS, Infect Dermatol & Allergol Unit, Rome, Italy

[4] Univ Roma La Sapienza, Dept Infect Dis, Rome, Italy

[5] Natl Inst Infect Dis Lazzaro Spallanzani IRCCS, Rome, Italy

[6] Univ Vita Salute San Raffaele, San Raffaele Hosp, Dept Infect & Trop Dis, Milan, Italy

[7] Amedeo Savoia Hosp, Infect & Trop Dis Unit, Turin, Italy

[8] Univ Perugia, Infect Dis Clin, Perugia, Italy

[9] Natl Inst Infect Dis Lazzaro Spallanzani IRCCS, Syst Infect & Immunodeficiency Unit, Rome, Italy

[10] Univ Sassari, Dept Clin & Expt Med, Sassari, Italy

[11] S Caterina Novella Hosp, Infect Dis Unit, Galatina, Italy

[12] Univ Milan, DIBIC Luigi Sacco, Infect Dis Unit, Milan, Italy

[13] SM Annunziata Hosp, Unit Infect Dis, Florence, Italy

[14] Azienda Osped Univ Senese, UOC Malattie Infett, Siena, Italy

[15] Univ Siena, Dept Med Biotechnol, Siena, Italy

来源：

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY | 2017年 / 72卷 / 04期

关键词：

HIV-INFECTED PATIENTS; NON-INFERIORITY TRIAL; PROTEASE INHIBITOR MONOTHERAPY; OPEN-LABEL; TRIPLE TREATMENT; DUAL TREATMENT; NAIVE ADULTS; EFFICACY; THERAPY; EMTRICITABINE;

D O I：

10.1093/jac/dkw557

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

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/mm(3). 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.

引用

页码：1163 / 1171

页数：9

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