Phase 4
N=52
IMPAACT P1092: Steady State PK in Malnourished HIV Infected Children
HIV Positive · Malnourished
Bottom Line
View on ClinicalTrials.gov: NCT01818258 ↗Enrolled (actual)
52
Serious AEs
26.9%
Results posted
Aug 2021
Primary outcome: Primary: Grade 3 or Higher Adverse Events Through 24 Weeks — 13; 10 Participants — p=0.40
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- ZDV+3TC+LPV/r (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- International Maternal Pediatric Adolescent AIDS Clinical Trials Group
- Primary completion
- Apr 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Grade 3 or Higher Adverse Events Through 24 Weeks |
13; 10 | 0.40 |
| PRIMARY Grade 3 or Higher Adverse Events Related to Study Drugs Through Week 24 |
6; 7 | >0.999 |
| PRIMARY Steady-state Lopinavir Area Under the Curve |
49.8; 64.8; 53.0; 83.4; 64.6; 79.4 | 0.49 |
| PRIMARY Plasma Clearance of Lopinavir |
2.2; 2.0; 2.3; 1.6; 2.1; 1.7 | 0.89 |
| PRIMARY Steady-state Ritonavir Area Under the Curve |
1.6; 2.1; 1.8; 3.0; 2.3; 3.0 | 0.42 |
| PRIMARY Plasma Clearance of Ritonavir |
16.9; 15.8; 17.3; 11.2; 14.8; 11.5 | 0.84 |
| PRIMARY Steady-state Lamivudine Area Under the Curve |
4,245.0; 5,520.2; 4,365.5; 7,233.0; 6,359.0; 5,849.2 | 0.27 |
| PRIMARY Plasma Clearance of Lamivudine |
8.7; 8.4; 9.5; 6.8; 7.5; 8.8 | 0.89 |
| PRIMARY Steady-state Zidovudine Area Under the Curve |
2,261.0; 1,774.0; 1,826.0; 1,335.7; 2,449.7; 1,609.3 | 0.39 |
| PRIMARY Plasma Clearance of Zidovudine |
34.8; 58.3; 48.8; 81.8; 40.8; 64.0 | 0.090 |
| SECONDARY Minimum Trough Concentration (Ctrough) of Lopinavir |
12; 21; 14; 18; 13; 18 | 0.17 |
| SECONDARY Free Fraction of LPV at Hour 2 Post Dose |
0.8; 3.2; 2.2; 6.0; 3.1; 2.1 | 0.003 sig |
| SECONDARY Change in HIV Viral Load From Baseline |
-1.4; -2.1; -1.7; -2.5; -1.8; -2.5 | 0.15 |
| SECONDARY HIV Viral Load <400 Copies/mL |
2; 2; 8; 14; 11; 18 | >0.999 |
| SECONDARY Change in CD4 Percent |
3.3; 3.0; 9.3; 6.8; 10.3; 7.1 | 0.89 |
| SECONDARY Change in WHO Weight-for-height Z-score |
2.3; 0.1; 2.7; 0.4 | <0.0001 sig |
| SECONDARY Change in Mid-upper Arm Circumference |
2.6; 1.2; 3.5; 1.6 | <0.0001 sig |
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 34.4 to 35.0 to 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.
Data sourced from ClinicalTrials.gov (NCT01818258). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.