A Prospective, Open-label Trial of Two ABC/3TC Based Regimens in Late Presenter naïve Patients (CD4 <200 Cells/µL)

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.

Timeline

Start

2013-11

Primary completion

2017-12

Completion

2017-12

Drugs

Indications