Clinical trial NCT01511809: Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression
Official title: Efficacy of Atazanavir / Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression. Randomized, Open Label Non Inferiority Trial. A Phase 3 Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV-1
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2012-01-19
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Proportion of Patients With Treatment Failure (TF)
timeFrame: Up to week 48
Secondary outcomes:
measure: Efficacy and Safety
timeFrame: week 96
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Infectious Diseases Department Fondazione Centro San Raffaele
state: Lombardia
Study officials:
affiliation: Ospedale San Raffaele
name: Adriano Lazzarin, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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