Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-infected Children On Long-term Suppressive Antiretroviral Therapy
Background. 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.Methods. 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.Results. 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).Conclusion. 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.
Melvin, A., Warshaw, M., Compagnucci, A., Saidi, Y., Harrison, L., Turkova, A., Tudor-Williams, G., & PENPACT-1 (PENTA 9/PACTG 390/ANRS 103) Study Team. (2017). Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-infected Children On Long-term Suppressive Antiretroviral Therapy. Journal of the Pediatric Infectious Diseases Society, 6 (3), e109-e115. https://doi.org/10.1093/jpids/pix050