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

French National Agency for Research on AIDS and Viral Hepatitis

Status and phase

Terminated

Phase 2

Conditions

HIV Infections

Treatments

Drug: Tenofovir

Drug: Ritonavir

Drug: Atazanavir

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00122577

ANRS 107 Puzzle 2

Details and patient eligibility

About

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.

Full 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

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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