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

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