IMPAACT P1092: Steady State PK in Malnourished HIV Infected Children
Condition: HIV Positive; Malnourished
MeSH terms: HIV Seropositivity; Malnutrition
Intervention: ZDV+3TC+LPV/r
Intervention MeSH terms: Ritonavir; Lopinavir; Lamivudine; Zidovudine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 6 Months
Maximum age: 36 Months
Healthy volunteers: No
Keywords: HIV; Children; HAART; Malnourished

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documentation of HIV-1 infection defined as positive results from two samples
             collected at different time points, using protocol-specified tests

          -  Meets WHO classification for severe malnutrition, normal nutrition status, or mild
             malnutrition

          -  Eligible for HAART defined by WHO 2013 pediatric guidelines

          -  Parent or legal guardian able and willing to provide signed informed consent, remain
             within the study area during the study period and agree to have subject followed at
             the clinical site

          -  Qualifying hematology and chemistry laboratory values obtained from specimens
             collected within the study-specific screening period

          -  For severely malnourished children: An inpatient in a nutrition rehabilitation unit.
             Clinical improvement after 10-18 days on nutrition rehabilitation defined as: Appetite
             returned and eating better - child shows interest in food even if does not complete
             amount given:

          -  No further weight loss

          -  Normalized sodium and potassium defined as severity grade 1 or lower

          -  No evidence of cardiac failure

          -  Loss of apathy and starting to play

          -  No hypothermia or pyrexia - temperature stable at >35.0 to <38.0° C (non-axillary) or
             >34.4 to <37.4° C (axillary)

        For children with normal - mild malnutrition, clinical stability will be indicated by:

          -  Good appetite

          -  Normalized sodium and potassium defined as severity grade 1 or lower

          -  No hypothermia or pyrexia - temperature stable at >35.0 to <38.0° C (non-axillary) or
             >34.4 to <37.4° C (axillary)

        Exclusion Criteria:

          -  Edematous malnutrition at the time of study entry

          -  ≥ Grade 3 respiratory distress or presence of cardio respiratory compromise within 3
             days prior to entry

          -  Chemotherapy for malignancy

          -  Acute infection for which the child has received appropriate antimicrobial treatment
             for <5 days

          -  Tuberculosis disease

          -  Clinic hepatitis as evidenced by jaundice and hepatomegaly

          -  Taking any disallowed medications

          -  Any condition, situation, or clinical finding that in the opinion of the investigator
             would place the child at an unacceptable level of risk for injury, or render the
             child/caregiver(s) unable to meet the requirements of the study, interfere with study
             participation, or in the interpretation of study results.