Phase 4
Completed N=52
IMPAACT P1092: Steady State PK in Malnourished HIV Infected Children
HIV Positive · Malnourished
Source: ClinicalTrials.gov NCT01818258 ↗
Enrolled (actual)
52
Serious AEs
26.9%
Results posted
Aug 2021
Primary outcomePrimary: Grade 3 or Higher Adverse Events Through 24 Weeks — 13; 10 Participants — p=0.40
◆ Published Evidence
Emerging
6citations · ~1 / year
Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092.
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.
Linked Publications (2)
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Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092.
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Micronutrients and nutritional status among children living with HIV with and without severe acute malnutrition: IMPAACT P1092.
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 |
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) and the linked publication. 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. Informational only — not medical advice.