Clinical trial NCT00016718
Conditions: HIV Infections
Keywords: Didanosine Drug Therapy, Combination Drug Administration Schedule Reverse Transcriptase Inhibitors Anti-HIV Agents Pharmacokinetics Deoxycytidine Efavirenz Treatment Naive
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2001-08-01; Completion date: 2009-01-01
Enrollment: 43 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: Emtricitabine (FTC), Efavirenz (EFV) and Didanosine (ddI) together once daily arm 2: Emtricitabine (FTC), Efavirenz (EFV) and Didanosine (ddI) together once daily arm 3: Emtricitabine (FTC), Efavirenz (EFV) and Didanosine (ddI) together once daily
Interventions: intervention 1: Didanosine (ddI) intervention 2: Efavirenz (EFV) intervention 3: Emtricitabine (FTC)
Intervention descriptions: intervention 1: Antiretroviral Didanosine (ddI) : 240 mg/m\^2 up to a maximum of 400 mg once daily intervention 2: 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 intervention 3: Antiretroviral Emtricitabine (FTC): 6 mg/Kg up to a maximum of 200 mg once daily

Protocol documents: