A Prospective, Open-label Trial of Two ABC/3TC Based Regimens in Late Presenter naïve Patients (CD4 <200 Cells/µL)
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 3

Summary: 
      1. PROTOCOL SUMMARY This is a prospective, randomized open-label, 2 arm, 3-phase trial to
      compare the 48-weeks virological response of two different regimens containing
      abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine
      + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care
      with CD4+ counts < 200/mm3.

      1.1 Clinical Objectives: Primary Objective: To compare the 48-week virological response to
      two different regimens containing abacavir/lamivudine (abacavir/lamivudine
      +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral
      therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

      Secondary Objective: a) To compare immunological response at 48 weeks; b) To determine the
      safety and tolerability of the 2 regimens.

      1.2 Study population: 350 in/out patients 1.3 Outcome Primary Endpoint

        -  Proportion of patients with HIV RNA<50 copies/mL after 48 weeks Secondary Endpoints(s)

        -  Change in CD4+ cell count from baseline through week 48

        -  Time to virological rebound 1.4 Study design: Multicentre, parallel group, randomised,
           open label, non-inferiority study 1.5 Treatment regimens: Arm A: abacavir/lamivudine 1
           tablet once a day + raltegravir 400 mg (1 tablet twice a day) Arm B: abacavir/lamivudine
           1 tablet once a day + ritonavir 100 mg + darunavir 800 mg once a day.

      All drugs have been approved for the treatment of HIV infection. The study population will
      consist of 350 HIV-positive, HLA B5701-negative patients. At baseline, patients will be
      randomized 1:1 to start abacavir/lamivudine plus either raltegravir or darunavir/ritonavir.
      Randomization will be stratified on the basis of the screening CD4+ cell count (≤100 vs ≥100
      cells/µL), to ensure balance across treatments groups 1.7 Criteria for Safety: Adverse events
      and laboratory assessments. 1.8 Statistical analysis: As this is a non-inferiority trial, we
      will calculate the difference in the proportions of patients experiencing the primary outcome
      in the two treatment arms and will calculate a 95% confidence interval for this.
      Non-inferiority of the raltegravir arm will be demonstrated if the lower limit of the 95%
      confidence interval is greater than -12%. In case non-inferiority will be met, analyses for
      superiority will be performed.
    

Detailed description: 
      1. PROTOCOL SUMMARY This is a prospective, randomized open-label, 2 arm, 3-phase trial to
      compare the 48-weeks virological response of two different regimens containing
      abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine
      + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care
      with CD4+ counts < 200/mm3.

      1.1 Clinical Objectives: Primary Objective: To compare the 48-week virological response to
      two different regimens containing abacavir/lamivudine (abacavir/lamivudine
      +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral
      therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

      Secondary Objective:

        1. To compare immunological response at 48 weeks;

        2. To determine the safety and tolerability of the 2 regimens. 1.2 Study population: 350
           inpatients or outpatients will be randomized 1.3 Outcome Primary Endpoint

             -  Proportion of patients with undetectable viremia (HIV RNA<50 copies/mL) after 48
                weeks Secondary Endpoints(s)

             -  Change in CD4+ cell count from baseline through week 48

             -  Time to virological rebound Safety endpoints

             -  Incidence of adverse events (AEs)

             -  Incidence of serious adverse events (SAEs)

             -  Discontinuations due to adverse events

             -  Incidence of grade 3 or 4 laboratory abnormalities. 1.4 Study design Multicentre,
                parallel group, randomised, open label, non-inferiority study 1.5 Planned sample
                size: The planned sample size for this trial is 350 patients 1.6 Treatment
                regimens: Arm A: abacavir/lamivudine 1 tablet once a day + raltegravir 400 mg (1
                tablet twice a day) Arm B: abacavir/lamivudine 1 tablet once a day + ritonavir 100
                mg + darunavir 800 mg once a day.

      All drugs have been approved for the treatment of HIV infection. Administration: oral The
      study population will consist of 350 HIV-positive, HLA B5701-negative patients. At baseline,
      patients will be randomized 1:1 to start abacavir/lamivudine plus either raltegravir or
      darunavir/ritonavir. Randomization will be stratified on the basis of the screening CD4+ cell
      count (≤100 vs ≥100 cells/µL), to ensure balance across treatments groups 1.7 Criteria for
      Safety: Adverse events and laboratory assessments. 1.8 Statistical analysis: As this is a
      non-inferiority trial, we will calculate the difference in the proportions of patients
      experiencing the primary outcome in the two treatment arms and will calculate a 95%
      confidence interval for this. Non-inferiority of the raltegravir arm will be demonstrated if
      the lower limit of the 95% confidence interval is greater than -12%. In case non-inferiority
      will be met, analyses for superiority will be performed.
    

Intervention name(s): abacavir/lamivudine + raltegravir; abacavir/lamivudine + darunavir/ritonavir
Intervention type(s): Drug; Drug
Intervention description(s): abacavir/lamivudine + raltegravir; abacavir/lamivudine + darunavir/ritonavir
Other intervention name(s): Kivexa; Isentress; Kivexa; Prezista; Norvir
Intervention MeSH terms: Ritonavir; Darunavir; Lamivudine; Raltegravir Potassium; Abacavir; Dideoxynucleosides
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: late presenter; naïve; advanced HIV disease