Clinical trial NCT00887120: Dose Reduction of Lopinavir in Children
Official title: Pharmacokinetics and Efficacy of Low- or Standard-dose of Lopinavir/Ritonavir (Kaletra®) in PI-naïve HIV-1 Infected Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
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.
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Ministry of Education, Thailand
First posted: 2009-04-23
Enrollment: 24
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: pharmacokinetics of standard vs low dose LPV/r
timeFrame: 4 weeks after start ART
Secondary outcomes:
measure: efficacy and safety of standard and low dose LPV/r
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok
Study officials:
affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University and Thai Red Cross Aids Research Centre - HIV-NAT
name: Kiat Ruxrungtham, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Puthanakit T, van der Lugt J, Bunupuradah T, Ananworanich J, Gorowara M, Phasomsap C, Jupimai T, Boonrak P, Pancharoen C, Burger D, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children. J Antimicrob Chemother. 2009 Nov;64(5):1080-6. doi: 10.1093/jac/dkp322. Epub 2009 Sep 2.