Effectiveness of Early or Delayed Addition of Hydroxyurea to a Three-Drug Anti-HIV Drug Combination Including Didanosine, in Advanced HIV Patients Who Failed a First or Second Anti-HIV Triple-Drug Therapy
The purpose of this study is to find out whether or not the addition of hydroxyurea to didanosine (ddI) and other anti-HIV medications will result in better control of HIV infection.
The Food and Drug Administration (FDA) has approved ddI for treating HIV infections. Hydroxyurea is approved for treating some cancers and blood disorders. It works against HIV-1 when combined with ddI. Researchers need to look at how well patients may respond to hydroxyurea in combination with ddI and other anti-HIV drugs, and at any side effects.
Biological: Tetanus Toxoid Vaccine
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||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.
|Study Chair:||David Asmuth|
|Study Chair:||Judith Feinberg|
|Study Chair:||Richard Pollard|