IMPAACT P1092: Steady State PK in Malnourished HIV Infected Children

• Status: Completed
• Trial end date: 2017-09-29
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Mental Health (NIMH)
• Treatments: Lamivudine; Lopinavir; Ritonavir; Zidovudine

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.