Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression

Efficacy of Atazanavir / Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression. Randomized, Open Label Non Inferiority Trial. A Phase 3 Study.

The study will assess whether Atazanavir/ritonavir monotherapy provides a non-inferior proportion of virological efficacy with respect to ATV/RTV + 2 NRTIs in patients with stable suppressed viremia and no prior virologic failures.

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.
• ECG;
• 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.

Inclusion Criteria:

• HIV infected patients
• age > 18 years
• On treatment with ATV/r plus 2 NRTIs for at least 48 weeks
• Virological suppression (HIV-RNA<50 c/ml) by at least 24 weeks with ATV/r plus 2 NRTIs
• No virologic failure after the initiation of the first antiretroviral therapy. Previous treatment changes due to toxicity or treatment simplifications will be permitted only if occurred with documented virological suppression.
• CD4 cells nadir >100 cells/µL
• PPI and H2-receptor antagonists as follows: the proton-pump inhibitors should not be used; if H2-receptor antagonists are co-administered, a dose equivalent to famotidine 20 mg BID should not be exceeded.

Exclusion Criteria:

• Pregnancy and breast feeding women
• AIDS defining events
• Evidence of active HBV infection (HBsAg positive)
• Previous virological failure
• History of resistance to ATV
• Use of contraindicated medications