Dose Reduction of Lopinavir in Children
- Conditions
- HIV Infections
- Interventions
- Drug: Lopinavir/ritonavir standard dose According to WHO simplified dosing tableDrug: Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)
- Registration Number
- NCT00887120
- Brief Summary
To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in ARV PI naive HIV-1 infected Thai children.
To study clinical and immunological efficacy after 48 weeks of lopinavir/ritonavir in PI naïve HIV-1 infected Thai children
- Detailed Description
In 2002, the Thai Ministry of Public Health (MOPH) launched the National Access to Antiretroviral Program for People living with HIV/AIDS (NAPHA) with the aim of providing treatment to all Thai patients who needed antiretroviral treatment. By the end of 2005, 80,000 HIV-infected Thais were treated in the NAPHA program, including about 6,000 children. The antiretroviral treatment regimen consists of three antiretroviral drugs (ARV). The first-line regimen used in NAPHA are mainly generic drugs produced by Thai government pharmaceutical organization (GPO), including a fixed-drug combination of stavudine, lamivudine, and nevirapine (GPOvir);and a fixed-drug combination of zidovudine, lamivudine, and nevirapine (GPOvir-Z). Majority of patients respond very well with first-line regimen(1,2), however about 15% of patients have drug resistance to first-line regimen and require second-line regimen(3). The protease inhibitors (PIs) is used as a second-line regimen, however there are limitations in terms of cost and metabolic complications(4).
Lopinavir/ritonavir is the most widely use protease inhibitors in children because of its high efficacy and a syrup formulation that easy to use in small children. There is evidence supported that the recommended dose according to US-FDA or EU guidelines resulting in much higher plasma blood level in Thai children. Data from 19 Thai children demonstrated Cmin of 5.9 mg/L compare to 3.4 mg/L in US children when use the same dose (the minimum acceptable Cmin is 1.0 mg/L) (5,6). There is a study HIVNAT019, which demonstrated acceptable LPV plasma concentration and treatment outcome in Thai HIV-infected adult when use reduced dose of LPV/r 266mg/66 mg compare to standard dose of 400mg/100mg (7).
Therefore, the study of pharmacokinetic of low dose of LPV/r in Thai HIV-infected children is very important to assess the safety and efficacy of this strategy. This will lead to appropriate ARV dose in children to reduce long-term adverse events, and also reduce the ARV cost.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- Age from 2- 18 years old
- Documented positive test for HIV-1 infection
- PI-naïve
- HIV RNA viral load > 1,000 copies
- Written informed consent
- Active opportunistic infection
- Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion.
- Use of concomitant medication that may interfere with the pharmacokinetics of lopinavir/ritonavir
- Pregnancy or lactating
- Inability to understand the nature and extent of the study and the procedures required.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Lopinavir/ritonavir standard dose According to WHO simplified dosing table Lopinavir/ritonavir standard dose + zidovudine and lamivudine 2 Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table) Lopinavir/ritonavir low dose (70% of standard dose) + zidovudine and lamivudine
- Primary Outcome Measures
Name Time Method pharmacokinetics of standard vs low dose LPV/r 4 weeks after start ART
- Secondary Outcome Measures
Name Time Method efficacy and safety of standard and low dose LPV/r 48 weeks
Trial Locations
- Locations (1)
HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok
🇹🇭Bangkok, Thailand