A Phase II, Double-Blind, Randomized Study to Determine the Effect of Adding Delayed Versus Immediate Hydroxyurea to a Genotypic Based, ddI-Containing, Three-Drug Antiretroviral Regimen on the Recovery of Total CD4+ T-Cell Counts and Suppression of Plasma Viral Load in Advanced HIV-1 Infected Subjects Failing a First or Second Triple Combination Therapy
Increasing frequency of treatment failures on potent antiretroviral therapy has accelerated
the need for new classes of agents. Hydroxyurea, an agent broadly used for its
antineoplastic properties, has been shown to inhibit HIV-1 in vitro and in vivo when
combined with the nucleoside analogue reverse transcriptase inhibitor didanosine (ddI).
There is an urgent need to prospectively test the safety, tolerability, and efficacy of
hydroxyurea in late-stage, treatment-experienced patients.
Patients undergo genotypic analysis after registration to Step 1. Genotypic antiretroviral
resistance test (GART) along with a patient's antiretroviral drug history will be used to
select an optimal antiretroviral drug regimen (non-study drugs) for each patient. Patients
willing to initiate the GART-based regimen are randomized at Week 5 into Step 2. They are
stratified, first by level of ddI resistance, then within each strata by CD4+ T cell count,
and then assigned to 1 of 3 treatment arms to start all study drugs (ddI and hydroxyurea)
and non-study antiretroviral drugs on the day of randomization. Patients in Arm A receive
ddI and hydroxyurea placebo; Arm B, ddI and hydroxyurea placebo that is replaced by
hydroxyurea after 8 weeks; and Arm C, ddI and hydroxyurea. Patients receive treatment for 48
weeks. Patients are checked regularly for immunologic, virologic, and metabolic parameters.
Patients may elect to participate in substudy A5070s, which explores the effects of study
treatment on T cell populations and other immunologic evaluations.
Endpoint Classification: Safety Study, Masking: Double-Blind, Primary Purpose: Treatment
United States: Federal Government