Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Efficacy of Atazanavir / Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression. Randomized, Open Label Non Inferiority Trial. A Phase 3 Study.|
- Proportion of Patients With Treatment Failure (TF) [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]Proportion of patients with treatment failure defined as having one of the following events: confirmed viral rebound (CVR) or treatment discontinuation for any cause. CVR was established when 2 consecutive viral load values (HIV-1 RNA)>50 copies/mL occurred within 2 weeks during follow-up. In case of CVR, patients treated with atazanavir/ritonavir monotherapy had to re-introduce their previous 2NRTIs (re-intensification) and, if not suppressed (HIV-1 RNA <50 copies /ml) after 12 weeks, discontinued from the study. Re-intensification was considered as treatment failure in the primary analysis conducted according to the intention-to-treat principle (intention-to-treat analysis with re-intensification equal failure, ITT=Failure) while it was not in the secondary analysis (intention-to-treat analysis with re-intensification equal success, ITT=Success).
- Efficacy and Safety [ Time Frame: week 96 ] [ Designated as safety issue: Yes ]
Proportion of pts with confirmed virological and treatment failure at w96. Change in CD4 cell counts.
Occurrence of viral resistance to atazanavir in pts with confirmed virologic failure.
Proportion of pts with adverse events, with ≥grade 2 adverse events or abnormal laboratory tests, proportion of pts with side effects leading to discontinuation.
Body fat redistribution and vertebral and femoral bone mineral density. Adherence changes; changes in HIV-associated neurocognitive disorders. Difference in levels of activated Tcells and pro-inflammatory cytokines between treatment groups.
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Atazanavir/ritonavir monotherapy
Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy
Drug: Atazanavir/ritonavir monotherapy
Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.
Other Name: ATV/r monotherapy
No Intervention: Atazanavir/ritonavir triple therapy
Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone
This is a randomised (1:1), multicentre, comparative, parallel-group, prospective, open label, non-inferiority controlled clinical trial.
Enrolled patients, taking an ATV/r based HAART and with stable HIV-RNA < 50c/ml (24 weeks), will be randomized to:
- continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs (according to the specific dosing schedule) as backbone (HAART arm) with ATV/r
- or simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy (Monotherapy arm) with ATV/r The study follow up will be 96 weeks after randomization and primary objective will be evaluated at week 48.
Patients will be followed every 4 weeks for the first 16 weeks, and then every 8 weeks until week 48, then every 12 weeks until week 96 or discontinuation ; at each visit the following evaluations will be performed:
- clinical assessment.
- routine laboratory tests (hematological tests and hematochemistry) including creatinine, phosphorus, calcium, alkaline phosphatase, gammaGT; urine analysis, lipid profile, level of HIV-RNA and CD4 cell counts.
During follow-up, at randomization, week 48, week 96 or discontinuation, patients will additionally undergo:
- Fat redistribution evaluation by DEXA (dual-energy X-ray absorptiometry
- Vertebral and femoral bone mineral density evaluation by DEXA.
- Glicate haemoglobin.
- Adherence assessment (questionnaire and/or pills counts).
- Neurocognitive evaluation [HIV-associated neurocognitive disorders (HANDs) evaluated by validated neuropsychological tests].
In case of viral rebound (defined as 2 consecutive measurement of HIV-RNA > 50 c/ml) patients will be immediately contacted in order to perform genotypic tests. Furthermore a plasma PK analysis will also be performed. Any patients with virological rebound will be selected for a reintensification therapy with NRTIs and if not suppressed after 12 weeks they will be discontinued.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01511809
|Infectious Diseases Department Fondazione Centro San Raffaele|
|Milan, Lombardia, Italy, 20127|
|Principal Investigator:||Adriano Lazzarin, Professor||Ospedale San Raffaele|