A Study of a Nucleoside Sparing Regimen in HIV-1 Infected Patients With Detectable Viremia
Condition: HIV-1 Infection
MeSH terms: Viremia
Study type: Interventional
Phase: Phase 2

Summary: 
      Research ipotesis is to assess the efficacy and safety of a nucleos(t)ide sparing regimen of
      atazanavir/ritonavir 300 mg /100 mg QD + Dolutegravir 50 mg QD for the management of
      virological failure in HIV-1 infected patients.

      The Primary Objective is to explore the 24-week efficacy of a nucleos(t)ide sparing regimen
      of atazanavir 300 mg QD/ ritonavir 100 mg QD + Dolutegravir 50 mg QD for the management of
      virologic failure in HIV-1 infected, integrase inhibitor-naïve subjects.
    

Detailed description: 
      Study design;

      • 24-week prospective, single-arm, monocentric, open label, pilot study Participants will be
      seen at screening, baseline, day 8 and at week 4, 8, 12, 16, 24.

      At each visit the following evaluations will be performed:

        -  clinical assessment.

        -  routine laboratory tests (hematological tests and clinical chemistry) including
           hemochromocytometric examination with leukocytic formula, creatinine, creatine kinase,
           transaminases, phosphorus, calcium, alkaline phosphatase, total and direct bilirubin,
           gammaGT, uric acid, lactate dehydrogenase, urine analysis, glucose, lipid profile,
           HIV-RNA and CD4 cell counts.

      Additional blood samples will be collected at each visit for storage and further
      determinations.

      During follow-up, at different timepoints, patients will additionally undergo:

        -  HbA1c and fasting insulin levels and HOMA-IR determination (baseline, week 12, week 24)

        -  Adherence assessment (questionnaire and/or pills counts) at week 4, 12 and 24.

        -  ECG (baseline and week 24)

      Protocol virologic failure is defined as

        -  < 1 log10 decrease in plasma HIV-1 RNA by week 12, with subsequent confirmation, unless
           plasma HIV-RNA < 200 copies/ml OR

        -  a confirmed rebound in plasma HIV-RNA levels ≥ 50 copies/ml after prior confirmed
           suppression to < 50 copies/ml OR a confirmed plasma increase in HIV-1 RNA levels >
           1log10 copies/ml above the nadir value where nadir is ≥ 50 copies/ml OR

        -  a plasma HIV-1 RNA level ≥ 50 copies/ml at week 24

      Subjects who meet a protocol-defined virologic failure during follow-up will be discontinued
      from the study.

      Patients who suppress HIV-1 RNA < 50 cp/ml before week 24 and have a viral blip ≥ 50
      copies/ml at week 24 will undergo a plasma HIV-1 RNA re-test to confirm the virologic
      failure. At virologic failure subjects will perform genotypic and phenotypic tests and a
      plasma determination of ATV and DTG Cthrough.

      No changes in study treatment are allowed with the exception of ritonavir (RTV)
      discontinuation in patients with hyperbilirubinemia and/or gastrointestinal adverse events
      judged as RTV-related by the Investigator. In this case, subjects will remain on study using
      the regimen ATV 400mg QD + DTG 50mg QD. The discontinuation of RTV will not be considered as
      treatment failure.

      In subjects with plasma HIV-RNA < 50 copies/ml at week 24, the study treatment will be
      successively provided by Italian National Health system.
    

Intervention name(s): atazanavir 300 mg + ritonavir 100 mg + dolutegravir 50 mg
Intervention type(s): Drug
Intervention description(s): Switch to single arm treatment atazanavir-ritonavir 300-100 mg + dolutegravir 50 mg therapy for 24 weeks
Other intervention name(s): Reyataz 300 mg + norvir 100 mg + tivicay 50 mg
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate; Dolutegravir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV-1