ArticleThe Pediatric infectious disease journal2018
Population Pharmacokinetics of Lopinavir in Severely Malnourished HIV-infected Children and the Effect on Treatment Outcomes.
Article in The Pediatric infectious disease journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.
- Influence of Malnutrition on the Pharmacokinetics of Drugs Used in the Treatment of Poverty-Related Diseases: A Systematic Review.Clinical pharmacokinetics · 2021Pooled it
- Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.The Journal of antimicrobial chemotherapy · 2020Pooled it
- Effect of the Timing of Antiretroviral Treatment Initiation on Outcomes in Children Living With Human Immunodeficiency Virus Admitted With Severe Acute Malnutrition.Journal of the Pediatric Infectious Diseases Society · 2021Trial
- Population pharmacokinetics of abacavir and lamivudine in severely malnourished human immunodeficiency virus-infected children in relation to treatment outcomes.British journal of clinical pharmacology · 2019Trial
- Prevalence and factors contributing to severe undernutrition in children on antiretroviral therapy (ART) drugs in Ilala District, Tanzania.Scientific reports · 2026Article
- Health-Related Physical Fitness Evaluation in HIV-Diagnosed Children and Adolescents: A Scoping Review.International journal of environmental research and public health · 2024Article
- Abacavir pharmacokinetics in African children living with HIV: A pooled analysis describing the effects of age, malnutrition and common concomitant medications.British journal of clinical pharmacology · 2022Article
- Strategies to Reduce Mortality Among Children Living With HIV and Children Exposed to HIV but Are Uninfected, Admitted With Severe Acute Malnutrition at Mulago Hospital, Uganda (REDMOTHIV): A Mixed Methods Study.Frontiers in pediatrics · 2022Article
- Drug-Drug Interactions of Infectious Disease Treatments in Low-Income Countries: A Neglected Topic?Clinical pharmacology and therapeutics · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundIn developing countries, malnutrition remains a common clinical syndrome at antiretroviral treatment (ART) initiation. Physiologic changes because of malnutrition and during nutritional recovery could affect the pharmacokinetics of antiretroviral drugs.
methodsHIV-infected children admitted with severe acute malnutrition were randomized to early or delayed initiation of lopinavir (LPV)/ritonavir, abacavir and lamivudine using World Health Organization weight band dosage charts. LPV concentrations were measured on day 1 and day 14. Thereafter, patients were followed-up to week 48. The population pharmacokinetics of LPV was described using NONMEM v7.3. Covariates were screened to assess their influence on the pharmacokinetics of LPV, and the relationship between pharmacokinetic variability and treatment outcomes were assessed.
resultsFive hundred and two LPV concentrations were collected from 62 pediatric patients 0.1-3.9 years of age (median: 0.9 years). Rifampin-based antituberculosis treatment and "super-boosted" LPV/ritonavir were prescribed in 20 patients. LPV disposition was well described by a one-compartment model with first-order elimination. Neither randomization to early or delayed ART, tuberculosis comedications nor anthropometrical measurements explained the pharmcokinetic variability. Allometrically scaled fat-free mass influenced apparent clearance (CL/F) and volume of distribution (Vd/F). Pharmacokinetic exposure did not correlate with virologic outcomes or death at 12 or 48 weeks.
conclusionsLPV pharmacokinetics was influenced by fat-free mass and not by timing of ART initiation or tuberculosis comedication in severely malnourished HIV-infected children. LPV pharmacokinetics was found to be highly variable and bioavailability greatly reduced, resulting in a high CL estimate in this population. The role of LPV dose adjustment should be further evaluated in severely malnourished children initiating ART.
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Registered trials
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