Switch to Unboosted Atazanavir With Tenofovir Study
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: atazanavir; atazanavir/ritonavir
Intervention description: switch to unboosted atazanavir 400 mg daily; Continue current regimen of atazanavir 300 mg/ ritonavir 100 mg daily
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No
Keywords: HIV; Anti-HIV Agents; HIV Protease Inhibitors

Summary:

      A drug-drug interaction between the anti-HIV drugs tenofovir DF (TDF) and atazanavir (ATZ)
      results in lower ATZ plasma levels when the drugs are given together, particularly in
      patients not taking ritonavir to boost ATZ levels. Lower plasma drug levels may make the
      anti-HIV regimen less effective in controlling the HIV virus levels in the blood. For this
      reason, current treatment guidelines recommend that ATZ always be boosted with ritonavir in
      regimens also containing TDF. However, withdrawal of ritonavir is often desirable given the
      tolerability and toxicity issues with this agent, even at the low dose (100 mg daily) used to
      boost ATZ. For example, ritonavir can cause stomach upset, nausea, diarrhea, high cholesterol
      levels, and liver enzyme abnormalities.

      However, there is evidence that plasma ATZ levels may not predict treatment success on
      unboosted ATZ regimens, particularly among people whose plasma HIV virus is already under
      control and unboosted ATZ is being used as a maintenance strategy. In the BC Centre for
      Excellence in HIV/AIDS Drug Treatment Program (DTP), nearly 100 patients originally treated
      with ritonavir-boosted ATZ + TDF (+ FTC or 3TC) are receiving successful maintenance therapy
      with unboosted ATZ and the same TDF-based backbone.

      The study will examine the hypothesis that switching to maintenance therapy with unboosted
      ATZ 400mg daily will have similar 48-week virologic efficacy to continuing ATZ/ritonavir
      300/100mg daily among HIV-infected adults with stable viral load suppression on regimens
      comprising ATZ/ritonavir 300/100mg daily with TDF plus either FTC or 3TC, despite potentially
      lower ATZ trough levels with the unboosted regimen. In other words, patients whose HIV viral
      load is undetectable while receiving TDF (+FTC or 3TC) and ATZ/ritonavir will continue to
      maintain an undetectable viral load after switching to unboosted ATZ without ritonavir, in
      the same proportions as those continuing on their boosted ATZ/ritonavir regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HIV infected adults at least 19 years of age

          2. Willing and able to provide informed consent to study participation

          3. Currently receiving a regimen including atazanavir 300mg/ritonavir 100mg daily with
             either tenofovir/emtricitabine (FTC) or tenofovir/lamivudine (3TC), for at least 3
             months

          4. Plasma viral load (VL) <40 copies/mL for at least 2 consecutive measurements including
             the screening value, and < 150 copies/mL continuously for at least 3 months prior to
             screening

          5. Current regimen is first antiretroviral regimen, or if not first regimen, no evidence
             of resistance to any nucleosides (NRTIs) or protease inhibitors (PIs) on previous
             resistance tests

          6. Any CD4

        Exclusion Criteria:

          1. Clinically significant intolerance or toxicity with current regimen precluding regimen
             continuation (e.g. intolerance/toxicity to ritonavir necessitating ritonavir
             discontinuation)

          2. pregnancy or breast-feeding

          3. antiretroviral regimen including any nonnucleoside reverse transcriptase inhibitor
             (nevirapine, efavirenz, or etravirine)

          4. antiretroviral regimen including any protease inhibitor other than atazanavir and
             ritonavir

          5. concomitant treatment with proton pump inhibitors, rifampin, St. John's wort, or
             garlic supplements. (Antacids and H2 receptor antagonists will be allowed provided
             their dosing is separated from atazanavir administration by at least 2 and 10 hours,
             respectively).