RAD-1: A Phase I/II Antiretroviral Management Algorithm for Pediatric Subjects of Four-Drug Combination Therapies Based on Prior Antiretroviral Experience

The Master RAD Protocol is based on the concept that optimal suppression of viral load in vivo will be achieved in patients with rapidly progressing or advanced HIV disease (RAD) using antiretroviral combinations inhibiting viral replication at distinct sites of action. Antiretroviral combinations are chosen with the hypothesis that simultaneous change to as many new agents as possible is necessary to maximally reduce plasma viral load. In this open-label, multicenter study patients are randomized into 1 of 4 groups based on prior antiretroviral experience. Each regimen consists of 4 drugs that include a combination of nucleoside reverse transcriptase inhibitors (stavudine, lamivudine, zidovudine, didanosine, zalcitabine) plus nevirapine (NVP), nelfinavir (NFV), or ritonavir (RTV). Patients must be naive to at least 2 of the 4 drugs in the regimen and at least 1 of the novel drugs must be NVP, NFV, or RTV. Prior to randomization to a NFV- or RTV-containing regimen, patients are stratified by HIV RNA (greater than or equal to 50,000 or less than 50,000) and must able to receive 2 or more novel drugs.