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Melvin, AJ; Warshaw, M; Compagnucci, A; Saidi, Y; Harrison, L; Turkova, A; Tudor-Williams, G; Tudor-Williams, G.
Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-Infected Children on Long-term Suppressive Antiretroviral Therapy.
J Pediatric Infect Dis Soc. 2017; 6(3):e109-e115-e109-e115 Doi: 10.1093/jpids/pix050 [OPEN ACCESS]
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Abstract:
Data on long-term toxicity of antiretroviral therapy (ART) in HIV-infected children are sparse. PENPACT-1 was an open-label trial in which HIV-infected children were assigned randomly to receive protease inhibitor (PI)- or nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. We examined changes in clinical, immunologic, and inflammatory markers from baseline to year 4 in the subset of children in the PENPACT-1 study who experienced viral suppression between week 24 and year 4 of ART. Liver enzyme, creatinine, and cholesterol levels and hematologic parameters were assessed during the trial. Cystatin C, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), d-dimer, and soluble CD14 (sCD14) were assayed from cryopreserved specimens. Ninety-nine children (52 on PI-based and 47 on NNRTI-based ART) met inclusion criteria. The median age at initiation of ART was 6.5 years (interquartile range [IQR], 3.7-13.4 years), and 22% were aged <3 years at ART initiation; 56% of the PI-treated children received lopinavir/ritonavir, and 70% of NNRTI-treated children received efavirenz initially. We found no evidence of significant clinical toxicity in either group; growth, liver, kidney, and hematologic parameters either remained unchanged or improved between baseline and year 4. Total cholesterol levels increased modestly, but no difference between the groups was found. IL-6 and hs-CRP levels decreased more after 4 years in the NNRTI-based ART group. The median change in IL-6 level was -0.35 pg/ml in the PI-based ART group and -1.0 in the NNRTI-based ART group (P = .05), and the median change in hs-CRP level was 0.25 µg/ml in the PI-based ART group and -0.95 µg/ml in the NNRTI-based ART group (P = .005). These results support the safety of prolonged ART use in HIV-infected children and suggest that suppressive NNRTI-based regimens can be associated with lower levels of systemic inflammation. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Find related publications in this database (using NLM MeSH Indexing)
Adolescent -
Anti-HIV Agents - therapeutic use
Antiretroviral Therapy, Highly Active -
Benzoxazines - therapeutic use
Biomarkers - blood
C-Reactive Protein - analysis
Child -
Child, Preschool -
Cholesterol - blood
Creatinine - blood
Cystatin C - blood
Drug Monitoring -
Europe -
Female -
Fibrin Fibrinogen Degradation Products -
HIV Infections - drug therapy
Humans -
Inflammation - metabolism
Interleukin-6 - blood
Kidney - drug effects
Kidney - metabolism
Lipopolysaccharide Receptors - blood
Liver - drug effects
Liver - enzymology
Liver - metabolism
Lopinavir - therapeutic use
Male -
North America -
Reverse Transcriptase Inhibitors - therapeutic use
Ritonavir - therapeutic use
Time Factors -
Treatment Outcome -

Find related publications in this database (Keywords)
antiretroviral therapy
children
HIV
toxicity
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