A5175: PEARLS Evaluation of the Efficacy of Once-Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor- Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Individuals

Full Title: A Phase IV, Prospective, Randomized, Open-Label Evaluation of the Efficacy of Once-Daily Protease Inhibitor and Once Daily Non-Nucleoside Reverse Transcriptase Inhibitor Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Individuals from Resource-Limited Settings (PEARLS) Trial

This trial was terminated May 7, 2012; it was conducted under the AIDS Clinical Trials Group (ACTG) and funded by the U.S. National Institutes of Health.

The trial was conducted in Brazil, Haiti, India, Malawe, Peru, South Africa, United States, Thailand, and Zimbabwe.

A5175 was a phase IV, randomized, open-label, three-arm antiviral efficacy trial designed to evaluate three antiretroviral (ARV) regimens for treatment naïve HIV-infected participants: one regimen containing two nucleoside reverse transcriptase inhibitors (NRTIs) + an HIV-1 protease inhibitor (PI) regimen, and two regimens each containing two NRTIs + a non-nucleoside reverse transcriptase inhibitor (NNRTI). 



The primary treatment comparisons in A5175 investigated:

1. 
   If a once-daily regimen containing two NRTIs + PI (Arm 1B) is not inferior to a twice-daily regimen containing two NRTIs + NNRTI (Arm 1A)
2. 
   If a once-daily regimen that contains two NRTIs + NNRTI (Arm 1C) is not inferior to a twice-daily regimen that also contains two NRTIs + NNRTI (Arm 1A).  

Both evaluations were based on the primary study endpoint, time to treatment failure of the initial regimens (Step 1). 



Time to treatment failure will be defined as the time from randomization to the first occurrence of any of the following: 1) death due to any cause; 2) disease progression - defined as a new or recurrent AIDS-defining opportunistic infection or malignancy occurring after completion of 12 weeks of ARV treatment; 3) virologic failure defined as two successive measurements of plasma HIV-1 RNA ≥1000 copies/mL, with the first measurement at week 16 or later. Participants who experience virologic failure on the Step 1 initial regimen may receive a second ARV regimen in Step 2.