Safety and Effectiveness of Emtricitabine, Efavirenz, and Didanosine in HIV Infected Children Who Have Taken Few or No Anti-HIV Drugs
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Treatment of HIV-infected patients involves combining drugs from different classes of
      anti-HIV drugs. One preferred regimen for adults is 2 nucleoside reverse transcriptase
      inhibitors (NRTIs) and 1 protease inhibitor (PI). For children, this regimen may be too
      complicated or the drugs may be too difficult to take by mouth. The purpose of this study was
      to determine the long-term safety and effectiveness of daily didanosine (ddI), efavirenz
      (EFV), and emtricitabine (FTC) in pediatric patients who had taken few or no anti-HIV drugs.
    

Detailed description: 
      Anti-HIV treatment options are limited for pediatric patients because combination therapies
      recommended for adults may not be appropriate for children or adolescents. Few PIs are
      available in formulations appropriate for pediatric patients, and complex dosing schedules
      and food requirements may be detrimental to treatment adherence. A once-daily regimen of the
      NRTIs ddI and FTC and the nonnucleoside reverse transcriptase inhibitor (NNRTI) EFV has been
      shown safe and well tolerated in adults.

      This Phase I/II open label study evaluated the long-term safety and efficacy of a ddI, FTC,
      and EFV regimen in pediatric patients. All study patients were either absolutely naive to
      antiretroviral therapy or had received less than or equal to 56 days perinatal prophylaxis or
      less than 7 days of cumulative antiretroviral therapy prior to study entry, and had a plasma
      screening plasma HIV-1 RNA levels >= 5000 copies/mL. This study was written to characterize
      the disposition of FTC, determine the PK data for ddI-EC QD, comparing the bio-availability
      of the enteric coated formulation with ddI pediatric powder for oral solution, and to provide
      insight into the age related pharmacokinetics differences observed in this and other studies.

      HIV infected pediatric patients were stratified into three age Groups: Group 1: 90 days to <3
      years of age; Group 2: 3 years to 12 years of age (inclusive); and Group 3: 13 to 21 years of
      age (inclusive). The initial study doses for the triple drug regimen was FTC, 6 mk/kg up to a
      maximum of 200 mg once daily, for EFV, the dose for age Group 1 was determined in PACTG 382
      and dose adjusted for body size, and the doses for age Groups 2 and 3 were defined in the
      dosing table of the protocol of up to a maximum of 600 mg once daily as a capsule or 720 mg
      as an oral solution; for ddI, 240 mg/m2 up to a maximum of 400 mg once daily. Comparison of
      age groups was not required as per the protocol.

      Patients were followed for a maximum of 192 weeks; all patients were to receive ddI, EFV, and
      FTC together once daily. Study visits occurred at study entry, Weeks 2,and 4, and every 4
      weeks thereafter. Blood collection, medical history assessment, and a physical exam occurred
      at all visits; urine collection occurred at selected visits. Intensive pharmacokinetic (PK)
      studies was done at Weeks 2 and 12 to determine if dose adjustments were required for any of
      the drugs. If virologic failure was determined, PK studies was repeated 4 weeks after
      adjustments in therapy. Parents or guardians were asked to complete treatment adherence
      questionnaires at some visits. Some patients were also asked to participate in an additional
      PK study after Week 16 or week 96.
    

Intervention name(s): Didanosine (ddI); Efavirenz (EFV); Emtricitabine (FTC)
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Antiretroviral Didanosine (ddI) : 240 mg/m^2 up to a maximum of 400 mg once daily; Antiretroviral For Age Group 1 Efavirenz (EFV): dose adjusted for body size and for Age Groups 2 and 3 Efavirenz (EFV): up to a maximum of 600 mg once daily as a capsule ot 720 mg as an oral solution; Antiretroviral Emtricitabine (FTC): 6 mg/Kg up to a maximum of 200 mg once daily
Other intervention name(s): Videx, Videx EC; Sustiva; Emtriva
Intervention MeSH terms: Emtricitabine; Efavirenz; Didanosine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Didanosine; Drug Therapy, Combination; Drug Administration Schedule; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Pharmacokinetics; Deoxycytidine; Efavirenz; Treatment Naive