Dose Reduction of Lopinavir in Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Lopinavir/ritonavir standard dose According to WHO simplified dosing table; Lopinavir/ritonavir low dose ( 70% of WHO recommended dosing table)
Intervention type(s): Drug; Drug
Intervention description(s): BW 6-7.9 kg: 1.5 mL oral q 12 hr
BW 8.0-16.9 kg: 2.0 ml oral q 12 hr
BW 17.0-19.9 kg: 2.5 ml oral q 12 hr
BW 20.0 - 24.9 kg: 3.0 ml oral q 12 hr
BW 25.0 - 29.9 kg: 3.5 ml oral q 12 hr
BW 30.0-34.9 kg: 4.0 ml oral q 12 hr
BW > 35 kg: 5.0 ml oral q 12 hr
Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r); BW 6-7.9 kg: 1.0 mL oral q 12 hr
BW 8.0-16.9 kg: 1.5 ml oral q 12 hr
BW 17.0-19.9 kg: 1.8 ml oral q 12 hr
BW 20.0 - 24.9 kg: 2.0 ml oral q 12 hr
BW 25.0 - 29.9 kg: 2.5 ml oral q 12 hr
BW 30.0-34.9 kg: 3.0 ml oral q 12 hr
BW > 35 kg: 3.5 ml oral q 12 h
Dose of Zidovudine (AZT) is 180-240 mg/m2 per dose every 12 hours Dose of Lamivudine (3TC) is 4 mg/kg every 12 hours Dose of Lopinavir/ritonavir (LPV/r)
Intervention MeSH terms: Ritonavir; Lopinavir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Second line treatment; therapeutic drug monitoring; Asia; LPV; children; pharmacokinetic; To study the pharmacokinetics of low-dose and standard dose, lopinavir/ritonavir in Protease inhibitor (PI)- naive HIV-1 infected Thai patients.; To study clinical and immunological efficacy after 48-weeks of lopinavir/ritonavir-based antiretroviral therapy in PI naive HIV-1 infected Thai patients.