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Insulin Resistance and Markers of Inflammation in HIV-infected Ugandan Children in the CHAPAS-3 Trial
Sahera Dirajlal-Fargo1, Victor Musiime, Adrian Cook
1From the *Case Western Reserve University, and†Rainbow Babies and Children's Hospital, Cleveland, Ohio; ‡Joint Clinical Research Centre, and §Makerere University College of Health Sciences, Kampala, Uganda; ¶MRC Clinical Trials Unit University College, and ‖Institute of Child Health University College, London, United Kingdom.
Insights
Antiretroviral therapy (ART) in HIV-infected Ugandan children led to significant changes in insulin resistance, measured by homeostatic model assessment of insulin resistance (HOMA-IR). These changes were linked to markers of inflammation, specifically monocyte activation.
Area of Science:
- Pediatrics
- Infectious Diseases
- Metabolic Disorders
Background:
- Metabolic complications in HIV-infected African children are understudied.
- The relationship between inflammation and metabolic changes in this population requires further investigation.
Purpose of the Study:
- To compare baseline and changes in insulin resistance (HOMA-IR) and inflammation markers over 48 weeks.
- To explore associations between HOMA-IR and inflammation in ART-naive Ugandan children.
Main Methods:
- A subset of 118 ART-naive Ugandan children from a clinical trial were randomized to zidovudine-, stavudine-, or abacavir (ABC)-based regimens.
- Insulin resistance (HOMA-IR) and inflammation markers were assessed at baseline and 48 weeks.
- Nonparametric and multivariable analyses were used to compare groups and assess associations.
Main Results:
- HOMA-IR showed significant changes from baseline across all ART arms at 48 weeks, with no significant between-group differences.
- Several inflammation markers decreased significantly, while soluble CD14 increased in the ABC arm.
- Changes in soluble CD163 were positively associated with changes in HOMA-IR.
Conclusions:
- Antiretroviral therapy significantly altered HOMA-IR in ART-naive Ugandan children after 48 weeks.
- Changes in HOMA-IR correlated with monocyte activation markers.
Background:
Few studies have investigated metabolic complications in HIV-infected African children and their relation with inflammation.
Methods:
We compared baseline and changes in insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] and in markers of inflammation over 48 weeks, in a subset of antiretroviral therapy (ART)-naive Ugandan children from the Children with HIV in Africa-Pharmacokinetics and Adherence/Acceptability of Simple Antiretroviral Regimens trial randomized to zidovudine-, stavudine- or abacavir (ABC)-based regimen. Nonparametric methods were used to explore between-group and within-group differences, and multivariable analysis to assess associations of HOMA-IR.
Results:
One-hundred eighteen children were enrolled, and median age (interquartile range) was 2.8 years (1.7-4.3). Baseline median HOMA-IR (interquartile range) was 0.49 (0.38-1.07) and similar between the arms. At week 48, median relative changes in HOMA-IR were 14% (-29% to 97%) in the zidovudine arm, -1% (-30% to 69%) in the stavudine arm and 6% (-34% to 124%) in the ABC arm (P ≤ 0.03 for all the arms compared with baseline, but P = 0.90 for between-group differences). Several inflammation markers significantly decreased in all study arms; soluble CD14 increased on ABC and did not change in the other 2 arms. In multivariate analysis, only changes in soluble CD163 were positively associated with HOMA-IR changes.
Conclusions:
In ART-naive Ugandan children, HOMA-IR changed significantly after 48 weeks of ART and correlated with monocyte activation.
