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

Information source: Ospedale San Raffaele
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV-1 Infection

Intervention: Atazanavir/ritonavir monotherapy (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Ospedale San Raffaele

Official(s) and/or principal investigator(s):
Adriano Lazzarin, Professor, Principal Investigator, Affiliation: Ospedale San Raffaele

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Proportion of Patients With Treatment Failure (TF)

Secondary outcome: Efficacy and Safety

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

Minimum age: 18 Years. Maximum age: 90 Years. Gender(s): Both.

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

Locations and Contacts

Infectious Diseases Department Fondazione Centro San Raffaele, Milan, Lombardia 20127, Italy
Additional Information

Related publications:

Delfraissy JF, Flandre P, Delaugerre C, Ghosn J, Horban A, Girard PM, Norton M, Rouzioux C, Taburet AM, Cohen-Codar I, Van PN, Chauvin JP. Lopinavir/ritonavir monotherapy or plus zidovudine and lamivudine in antiretroviral-naive HIV-infected patients. AIDS. 2008 Jan 30;22(3):385-93. doi: 10.1097/QAD.0b013e3282f3f16d.

Cameron DW, da Silva BA, Arribas JR, Myers RA, Bellos NC, Gilmore N, King MS, Bernstein BM, Brun SC, Hanna GJ. A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination therapy. J Infect Dis. 2008 Jul 15;198(2):234-40. doi: 10.1086/589622.

Pulido F, Arribas JR, Delgado R, Cabrero E, González-García J, Pérez-Elias MJ, Arranz A, Portilla J, Pasquau J, Iribarren JA, Rubio R, Norton M; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV. AIDS. 2008 Jan 11;22(2):F1-9.

Arribas JR, Delgado R, Arranz A, Muñoz R, Portilla J, Pasquau J, Pérez-Elias MJ, Iribarren JA, Rubio R, Ocampo A, Sánchez-Conde M, Knobel H, Arazo P, Sanz J, López-Aldeguer J, Montes ML, Pulido F; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):147-52. doi: 10.1097/QAI.0b013e3181a56de5.

Arribas JR, Horban A, Gerstoft J, Fätkenheuer G, Nelson M, Clumeck N, Pulido F, Hill A, van Delft Y, Stark T, Moecklinghoff C. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS. 2010 Jan 16;24(2):223-30. doi: 10.1097/QAD.0b013e3283348944.

Katlama C, Valantin MA, Algarte-Genin M, Duvivier C, Lambert-Niclot S, Girard PM, Molina JM, Hoen B, Pakianather S, Peytavin G, Marcelin AG, Flandre P. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS. 2010 Sep 24;24(15):2365-74. doi: 10.1097/QAD.0b013e32833dec20.

Swindells S, DiRienzo AG, Wilkin T, Fletcher CV, Margolis DM, Thal GD, Godfrey C, Bastow B, Ray MG, Wang H, Coombs RW, McKinnon J, Mellors JW; AIDS Clinical Trials Group 5201 Study Team. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression. JAMA. 2006 Aug 16;296(7):806-14.

Karlström O, Josephson F, Sönnerborg A. Early virologic rebound in a pilot trial of ritonavir-boosted atazanavir as maintenance monotherapy. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):417-22.

Wilkin TJ, McKinnon JE, DiRienzo AG, Mollan K, Fletcher CV, Margolis DM, Bastow B, Thal G, Woodward W, Godfrey C, Wiegand A, Maldarelli F, Palmer S, Coffin JM, Mellors JW, Swindells S. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: final 48-week clinical and virologic outcomes. J Infect Dis. 2009 Mar 15;199(6):866-71. doi: 10.1086/597119.

Vernazza P, Daneel S, Schiffer V, Decosterd L, Fierz W, Klimkait T, Hoffmann M, Hirschel B. The role of compartment penetration in PI-monotherapy: the Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial. AIDS. 2007 Jun 19;21(10):1309-15.

Starting date: September 2010
Last updated: November 17, 2014

Page last updated: August 23, 2015

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