Open AccessSimplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV‐infected patients: 24‐weeks interim analysis from ATLAS‐M trial
Author(s) -
Fabbiani Massimiliano,
Di Giambenedetto Simona,
QuirosRoldan Eugenia,
Latini Alessandra,
Vullo Vincenzo,
Antinori Andrea,
Castagna Antonella,
Orofino Giancarlo,
Francisci Daniela,
Grilli Elisabetta,
Madeddu Giordanu,
Grima Pierfrancesco,
Rusconi Stefano,
Del Pin Barbara,
Mondi Annalisa,
Borghetti Alberto,
Focà Emanuele,
Colafigli Manuela,
De Luca Andrea,
Cauda Roberto
Publication year - 2014
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.17.4.19808
Subject(s) - medicine , atazanavir , ritonavir , lamivudine , interim analysis , regimen , clinical endpoint , viral load , randomized controlled trial , human immunodeficiency virus (hiv) , gastroenterology , surgery , antiretroviral therapy , virology , virus , hepatitis b virus
We report interim 24‐weeks efficacy data of ATLAS‐M trial, a phase IV, multicentre, open‐label, randomized study designed to show 48‐weeks, non‐inferior efficacy (margin of −12%) of treatment simplification to atazanavir/ritonavir (ATV/r)+lamivudine (3TC) versus maintaining 3‐drugs ATV/r‐based cART. Methods Subjects on ATV/r+2 NRTIs, without previous treatment failure (TF), with HIV‐RNA <50copies/mL for >3 months and CD4>200 cells/mm 3 for >6 months were eligible. At baseline, patients were randomized to switch to ATV/r+3TC (arm one) or to maintain the original 3‐drug regimen (arm two). Primary endpoint: proportion of patients free of TF at week 48. TF was defined as treatment modification for any reason, including virological failure (VF=two consecutive HIV‐RNA>50 copies/mL or a single value >1000 copies/mL). Enrollment of 266 patients was planned. Results A total of 266 patients (78% males, median age 44 years, median CD4 603 cells/µL, 79% treated with a tenofovir‐containing backbone) were enrolled. At the time of analysis, 24 weeks data were available for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 24 weeks, at the intention to treat analysis the proportion of patients free of TF was 91.7% (95% CI 85.8–97.6) and 85.1% (95% CI 77.6–92.6) in arm one and two, respectively (difference +6.6%, 95% CI −2.9/+16.1). VF was observed in two patients randomized to arm one (one at baseline, before treatment simplification) and one to arm two without resistance mutations. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 24, patients in arm one showed a greater increase in CD4 (mean change +90 vs +10 cells/µL, p=0.007). A greater increase in total cholesterol (+18 vs −2 mg/dL, p<0.001), HDL (+4 vs +0 mg/dL, p=0.001) and LDL (+12 vs +0 mg/dL, p=0.001) was also observed in arm one without differences in other lipid parameters. Renal function showed a significant improvement in arm one (mean change in eGFR +5 vs −2 mL/min/1.73m 2 in arm two, p=0.001). No significant differences in bilirubin levels or other laboratory parameters were observed between the two arms. Conclusions This interim analysis suggests a 24‐weeks non‐inferior efficacy of treatment simplification to ATV/rit+3TC as compared to continuation of ATV/rit +2 NRTI in virologically suppressed patients. Follow‐up until 48‐weeks is scheduled to confirm these data.