IMPAACT P1092: Steady State PK in Malnourished HIV Infected Children
Condition: HIV Positive; Malnourished
MeSH terms: HIV Seropositivity; Malnutrition
Study type: Interventional
Phase: Phase 4

Summary: 
      Children living with HIV from sub-Saharan Africa often present with severe malnutrition. In
      severe malnutrition, metabolic and/or gut structural derangement may lead to inadequate
      antiretroviral (ARV) absorption and/or erratic drug levels. The greater surface area to
      weight ratio in severely malnourished children could also place them at higher risk of under
      dosing compared to children with mild to moderate malnutrition. However, limited data are
      available on the pharmacokinetics of ARVs in severely malnourished children. This study
      addressed this critical gap in knowledge by evaluating the PK of zidovudine (ZDV), lamivudine
      (3TC), and lopinavir/ritonavir (LPV/r) in severely malnourished children living with HIV,
      compared to children with normal nutrition to mild malnutrition living with HIV.
    

Detailed description: 
      P1092 was a prospective, non-randomized Phase IV open label study of antiretroviral drugs
      zidovudine (ZDV), lamivudine (3TC), and ritonavir boosted lopinavir (LPV/r) in children
      living with HIV aged 6 to less than 36 months grouped by nutritional status. The study's
      primary objectives were to characterize the pharmacokinetics (PK), safety, and tolerability
      of antiretroviral (ARV) regimens in severely acute malnourished (SAM) children following the
      initiation of nutritional rehabilitation and compare results to mildly malnourished or
      normally nourished children in order to determine if current recommended doses are optimal in
      severely malnourished children.

      Two cohorts of children were enrolled based on nutritional status at screening: severely
      acute malnourished children and children with mild malnutrition or normal nutrition (non-SAM
      cohort). SAM participants were recruited from nutritional rehabilitation clinics while
      non-SAM participants were enrolled from HIV treatment centers. SAM participants were required
      to complete a 10 to 18 day nutritional rehabilitation program before entering the study. A
      World Health Organization (WHO, 2013) approach to management of SAM was used. All
      participants were to receive an antiretroviral regimen of ZDV+3TC+LPV/r. ARVs were dosed
      based on WHO weight band dosing and were to be administered twice per day in a pediatric
      liquid formulation. ZDV was allowed to be replaced with abacavir at the discretion of the
      site investigator/clinician in cases of grade 3 or higher hematologic toxicity on a
      ZDV-inclusive regimen or ZDV intolerance. Participants were followed for 48 weeks.
    

Intervention name(s): ZDV+3TC+LPV/r
Intervention type(s): Drug
Other intervention name(s): Zidovudine; Retrovir; Lamivudine; Epivir; Lopinavir/ritonavir; Kaletra
Intervention MeSH terms: Ritonavir; Lopinavir; Lamivudine; Zidovudine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV; Children; HAART; Malnourished