Efficacy and Safety of Tenofovir DF/Atazanavir Enhanced With Low Dose of Ritonavir in HIV-Infected Patients

NCT ID: NCT00122577

Last Updated: 2005-07-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-03-31
• Study Completion Date: 2004-07-31

Brief Summary

This trial is aimed at studying the antiviral activity, toxicity and pharmacokinetic (PK) interactions of tenofovir DF and atazanavir enhanced with low dose of ritonavir given alone and then concomitantly as part of a salvage regimen to HIV patients with multiple failure, under conditions allowing to tease out the specific role of atazanavir combined with low dose of ritonavir.

Detailed Description

When licensed, new drugs are widely used in patients failing antiretroviral therapy, including patients with multiple failures. In such patients, having multi-resistant virus, the introduction of one new drug only in the salvage regimen will infrequently result in undetectable virus load in the plasma. Tenofovir DF and atazanavir appear promising because of their pharmacokinetic profile, activity, safety and resistance properties. In addition, pharmacokinetic data in healthy volunteers suggest that atazanavir could be optimized by adding ritonavir at low dose. Thus, one may speculate that atazanavir pharmacokinetic and antiviral activity could be optimized by adding ritonavir at low dose in patients exhibiting high rate of protease inhibitor mutations.

This protocol is aimed at studying the antiviral activity, toxicity and PK interactions, of tenofovir DF and atazanavir enhanced with low dose of ritonavir given alone and then concomitantly as part of a salvage regimen to patients with multiple failure, under conditions allowing to tease out the specific role of atazanavir combined with low dose of ritonavir.

EKG abnormalities (increased PR and QTc intervals) were observed in normal volunteers treated with atazanavir, therefore EKG safety monitoring will be performed on all subjects during this study

Conditions

HIV Infections

Keywords

HIV infections; Treatment Failure; tenofovir; atazanavir

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Tenofovir

Intervention Type: DRUG

Atazanavir

Intervention Type: DRUG

Ritonavir

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males and non pregnant females 18 years of age and older who have confirmed laboratory diagnosis of HIV infection and documented failure (plasma HIV RNA level over 10,000 copies/ml) to at least two protease inhibitors (ritonavir [RTV] must have been given at a dose over 400 mg twice a day (bid), in order to qualify for a protease inhibitor in this study) and one non-nucleoside reverse transcriptase inhibitor (NNRTI)
• Ongoing antiretroviral therapy at inclusion without change within the last month
• No threshold of CD4 cell count
• Patients naive of atazanavir and tenofovir DF

Exclusion Criteria

• Cardiomyopathy
• QTc interval over 450 msec and pause length over 3 seconds on screening EKG
• Heart rate below 40 bpm
• Third degree heart block, and clinical symptoms potentially related to heart block
• Ongoing immunotherapy including IL2, interferon or HIV specific vaccine
• Ongoing opportunistic infection

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

French National Agency for Research on AIDS and Viral Hepatitis

OTHER_GOV

Sponsor Role: lead

Principal Investigators

Christophe Piketty, MD

Role: PRINCIPAL_INVESTIGATOR

Hopital Européen Georges Pompidou Paris, service d'immunologie clinique

Jean Pierre Aboulker, MD

Role: STUDY_CHAIR

Inserm SC10

Locations

Service d'Immunologie clinique Hopital Europeen Georges Pompidou

Paris, , France

Countries

France

References

Piketty C, Gerard L, Chazallon C, Calvez V, Clavel F, Taburet AM, Girard PM, Aboulker JP; ANRS 107 Puzzle 2 Study Group. Virological and immunological impact of non-nucleoside reverse transcriptase inhibitor withdrawal in HIV-infected patients with multiple treatment failures. AIDS. 2004 Jul 2;18(10):1469-71. doi: 10.1097/01.aids.0000131340.68666.21.

Reference Type: RESULT

PMID: 15199325 (View on PubMed)

Taburet AM, Piketty C, Chazallon C, Vincent I, Gerard L, Calvez V, Clavel F, Aboulker JP, Girard PM. Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2004 Jun;48(6):2091-6. doi: 10.1128/AAC.48.6.2091-2096.2004.

Reference Type: RESULT

PMID: 15155205 (View on PubMed)

Other Identifiers

ANRS 107 Puzzle 2

Identifier Type: -

Identifier Source: org_study_id