ABSTRACT. Objective. To assess the effects of antiretroviral combination therapy that contains protease inhibitor (PI) on carbohydrate and lipid metabolism in human immunodeficiency virus (HIV)-infected children.Methods. A cross-sectional, descriptive clinical study was conducted in an outpatient clinic. Thirty-seven HIVinfected children who ranged from 1 to 17 years of age received nucleoside reverse transcriptase inhibitor treatment together with PI (PI group, n ؍ 25) or without PI (non-PI group, n ؍ 12). Age, gender, weight, length, CD4 cell count, and viral load did not differ between groups. Nonfasting total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, glucose, lactate, and blood gases were determined. In addition, c-peptide, insulin, hemoglobin A1c, free fatty acids, lipoprotein a, and apolipoproteins A1 and B were evaluated after fasting. PI and non-PI group values were compared with normal values taken from healthy children.Results. In nonfasting and fasting conditions, children of the PI group had higher total cholesterol (fasting PI group: 235 ؎ 71 mg/dL; non-PI group: 176 ؎ 25 mg/dL, mean ؎ standard deviation), triglycerides (156 ؎ 89 vs 87 ؎ 31 mg/dL), and LDL cholesterol levels (159 ؎ 58 vs 113 ؎ 23 mg/dL) compared with the non-PI group. Highdensity lipoprotein cholesterol and apolipoprotein A1 levels did not differ in both groups; there was a trend toward higher apolipoprotein B levels in the PI group. After fasting, 8 (47%) of 17 patients in the PI group presented with hypercholesterolemia as a result of an increase of LDL cholesterol and 11 (65%) had hypertriglyceridemia. It is interesting that the non-PI group showed no pathologic deviations. Compared with normal values, lipoprotein a and free fatty acids were increased in the PI and non-PI groups. Glucose, lactate, blood gases, c-peptide, insulin, and hemoglobin A1c were normal in both groups.Conclusion. PI-containing antiretroviral treatment of HIV-infected children was associated with hypercholesterolemia, hypertriglyceridemia, and an increase of LDL cholesterol. The long-term complications of dyslipidemia are of major concern in the growing HIV-infected child. Pediatrics 2002;110(5). URL: http://www.pediatrics. org/cgi/content/full/110/5/e56; antiretroviral therapy, HIV infection, dyslipidemia, carbohydrate metabolism.ABBREVIATIONS. HAART, highly active antiretroviral therapy; PI, protease inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; HIV, human immunodeficiency virus; 3TC, lamivudine; AZT, zidovudine; NFV, nelfinavir; DDI, didanosine; d4T, stavadine; RTV, nitonavir, ABC, abacavir; DDC, zalcitabine; SAQ, saquinavir; HDL, high-density lipoprotein; LDL, low-density lipoprotein; Lp(a), lipoprotein a; HbA1c, hemoglobin A1c. H ighly active antiretroviral therapy (HAART) that consists of protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) in combination with nucleoside reverse tran...
The increased dose of 300/75 mg/m2 twice-daily lopinavir/ritonavir compensates for the enzyme-inducing effect of efavirenz in HIV-infected children.
Phosphatidylserine molecules are translocated to the outer plasma membrane of lymphocytes undergoing apoptosis and can be detected by the binding of fluorochrome-conjugated annexin V. Using the annexin V assay, we examined CD4 and CD8 T cells from human immunodeficiency virus (HIV)-infected children for apoptosis upon isolation or following in vitro culture. Immediate ex vivo analysis or overnight culture showed significantly higher levels of apoptosis in CD8 cells than in CD4 cells. Following culture with the activating stimulus phytohemagglutinin or anti-CD3 monoclonal antibody, we observed an increase in the percentage of apoptotic CD4 cells, whereas there was no change in the rate of CD8 cell death. These results demonstrate that in HIV-infected children, CD8 apoptosis may occur at a greater rate than CD4 apoptosis in vivo; greater CD4 depletion may be observed due to more efficient mechanisms for peripheral lymphocyte replacement in the CD8 compartment. Furthermore, our data suggest that CD8 lymphocytes may be maximally activated in vivo, a condition which may lead to the exhaustion of CD8-mediated immunity. These findings clarify the differences between the CD4 and CD8 apoptotic responses to HIV.
Increased apoptosis of lymphocytes represents a key event of immune destruction in HIV infection. In this study it was investigated at which stage of the disease and in which T lymphocyte subpopulation (CD4+ or CD8+) protection against apoptosis may be lost as measured by decreased CD28 expression. In 26 HIV-infected and 20 healthy children, as well as 10 infants exposed to HIV, expression of CD28 and the apoptosis-related marker CD95 was studied by fluorescence-activated cell sorting analysis. According to established Centers for Disease Control and Prevention definitions, children were divided into three immunologic categories. In the CD8 population, patients in category 1 already showed a markedly decreased mean CD28 (36.2%+/-16.1 SD) and increased CD95 expression (48.8+/-24.1%), compared with the age-matched control group (67.7+/-14.4%, 15.8+/-8.9%). In the CD4 population, mean CD28 and CD95 expression was not altered in category 1 patients. Of the exposed children, the child with the lowest CD28 expression on CD8 cells was determined later to be infected with HIV. Significant immunophenotypical alterations are observed in early stage pediatric HIV infection, which may indicate an early loss of protection against apoptosis in the CD8+ T cell population.
Despite effective HAART, electrophysiological motor testing in HIV (+) children reveals significant subclinical CNS dysfunction, especially in children with insufficient viral load suppression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.