Safety and Effectiveness of Four Anti-HIV Drug Combinations in HIV-Infected Children and Teens
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to see if it is safe and effective to give HIV-infected children
      and teens 1 of 4 anti-HIV drug combinations.

      Decreasing HIV levels in infected patients can slow down disease progression. Further study
      is needed to find out which drug combinations are most effective in doing this.
    

Detailed description: 
      For PRAM 2: Evidence suggests that as a consequence of antiviral therapy, decreases in plasma
      HIV-1 RNA are strongly associated with a delay in clinical progression. Therefore, the drug
      regimens proposed in this study are designed to result in a much larger sustained drop in
      plasma HIV-1 RNA and greater clinical benefit. Further intent of this study is to evaluate
      the virologic and therapeutic potential of novel combinations of antiretrovirals and to
      better define the pharmacokinetics and drug-drug interactions of therapies included in this
      regimen.

      The Master PRAM schema is designed to allow new therapeutic arms to be studied as "rolling
      screens" through multiple generations of PRAMs. There is a common, "linking" regimen between
      any 2 sequential PRAM generations that will permit an indirect comparison of included
      therapies. (NOTE: Due to significant changes in study design between PRAM 1 and PRAM 2, there
      is no "linking" arm between them. The linkage will be reinstated from PRAM 2 and subsequent
      PRAM generations.) The therapeutic potential of the treatment arms is assessed by their
      ability to decrease HIV copy numbers as defined by plasma HIV-1 RNA copy number. Once accrual
      to a PRAM is complete, a new treatment comparison will open for accrual.

      For PRAM 2: This study will compare the following 4 treatment arms:

      Arm A - stavudine (d4T)/nevirapine/ritonavir Arm B - d4T/lamivudine (3TC)/nelfinavir Arm C -
      d4T/nevirapine/nelfinavir Arm D - d4T/3TC/nevirapine/nelfinavir. Prior to randomization to 1
      of the PRAM 2 treatment arms, patients are stratified based on their CD4% (less than 25% and
      greater than or equal to 25%) and by age (less than 24 months and greater than or equal to 24
      months). The first 35 subjects/treatment arm are evaluated with special immunologic studies
      including lymphoproliferative assays and extended panel immunophenotyping. There is an
      interim analysis after all patients have completed 12 weeks of treatment. Patients are
      treated for 48 weeks. [AS PER AMENDMENT 6/11/99: The study has been extended for an
      additional 48 weeks (96 weeks total) to permit long-term follow-up of clinically stable,
      HIV-infected children.]
    

Intervention name(s): Ritonavir; Nelfinavir mesylate; Nevirapine; Lamivudine; Stavudine
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Ritonavir; Nelfinavir; Lamivudine; Nevirapine; Stavudine
Primary purpose: Treatment
Keywords: Drug Therapy, Combination; Nevirapine; Stavudine; HIV Protease Inhibitors; Ritonavir; Lamivudine; Nelfinavir; Reverse Transcriptase Inhibitors