dose reduction of lopinavir in children

Conditions: HIV Infections

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

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.

Eligibility criteria:
inclusion criteria: * 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 exclusion criteria: * 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.

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.