efficacy of atazanavir/ritonavir monotherapy as maintenance in patients with viral suppression

Conditions: HIV-1 Infection

Summary: 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.

Eligibility criteria:
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

Keywords: hiv-1