Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
Management of Medication Toxicity or Intolerance
Insulin Resistance, Asymptomatic Hyperglycemia, Diabetes Mellitus
Last Updated: April 27, 2017; Last Reviewed: April 27, 2017
|Adverse Effects||Associated ARVs||Onset/ Clinical Manifestations||Estimated Frequency||Risk Factors||Prevention/ Monitoring||Management|
|Insulin Resistance, Asymptomatic Hyperglycemia, DMa||ZDV
Rarely other PIs
Weeks to months after beginning therapy
|Risk Factors for Type 2 DM:
||Counsel on lifestyle modification (e.g., a diet low in saturated fat, cholesterol, transfat, and refined sugars; increased physical activity; cessation of smoking); consultation with dietician.
Change NRTI backbone (e.g., from ZDV, d4T, or ddI to TAF, TDF, or ABC).
For Either RPG ≥200 mg/dL plus Symptoms of DM or FPG ≥126 mg/dL:
Impaired FPG is suggestive of insulin resistance; consult endocrinologist.
FPG <100 mg/dL:
Normal FPG, but Does Not Exclude Insulin Resistance:
|a Insulin resistance, asymptomatic hyperglycemia, and DM form a spectrum of increasing severity. Insulin resistance is often defined as elevated insulin levels for the level of glucose observed; impaired FPG as an FPG of 100–125 mg/dL; impaired glucose tolerance as an elevated 2-hour PG of 140–199 mg/dL in a 75 g-OGTT (or if <43 kg, 1.75 g/kg of glucose up to a maximum of 75 g); and diabetes mellitus as either an FPG ≥126 mg/dL, a random PG ≥200 mg/dL in a patient with hyperglycemia symptoms, an HgbA1C of ≥6.5%, or a 2-hour PG after OGTT ≥200 mg/dL. However, the Panel does not recommend routine determinations of insulin levels, HgbA1C, or glucose tolerance without consultation with an endocrinologist; these guidelines are instead based on the readily available random and fasting plasma glucose levels.
Key to Acronyms: ABC = abacavir; ARV = antiretroviral; BMI = body mass index; d4T = stavudine; ddI = didanosine; dL = deciliter; DM = diabetes mellitus; FPG = fasting plasma glucose; HgbA1c = glycosylated hemoglobin; IDV = indinavir; LPV/r = lopinavir/ritonavir; NRTI = nucleoside reverse transcriptase inhibitor; OGTT = oral glucose tolerance test; PG = plasma glucose; PI = protease inhibitor; RPG = random plasma glucose; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; ZDV = zidovudine
- Bitnun A, Sochett E, Dick PT, et al. Insulin sensitivity and beta-cell function in protease inhibitor-treated and -naive human immunodeficiency virus-infected children. The Journal of Clinical Endocrinology and Metabolism. 2005;90(1):168-174. Available at http://www.ncbi.nlm.nih.gov/pubmed/15483082.
- Hadigan C. Insulin resistance among HIV-infected patients: unraveling the mechanism. Clin Infect Dis. 2005;41(9):1341-1342. Available at http://www.ncbi.nlm.nih.gov/pubmed/16206113.
- Morse CG, Kovacs JA. Metabolic and skeletal complications of HIV infection: the price of success. JAMA. 2006;296(7):844-854. Available at http://www.ncbi.nlm.nih.gov/pubmed/16905789.
- Aldrovandi GM, Lindsey JC, Jacobson DL, et al. Morphologic and metabolic abnormalities in vertically HIV-infected children and youth. AIDS. 2009;23(6):661-672. Available at http://www.ncbi.nlm.nih.gov/pubmed/19279441.
- Chantry CJ, Hughes MD, Alvero C, et al. Lipid and glucose alterations in HIV-infected children beginning or changing antiretroviral therapy. Pediatrics. 2008;122(1):e129-138. Available at http://www.ncbi.nlm.nih.gov/pubmed/18519448.
- Samaras K. Prevalence and pathogenesis of diabetes mellitus in HIV-1 infection treated with combined antiretroviral therapy. J Acquir Immune Defic Syndr. 2009;50(5):499-505. Available at http://www.ncbi.nlm.nih.gov/pubmed/19223782.
- Geffner ME, Patel K, Miller TL, et al. Factors associated with insulin resistance among children and adolescents perinatally infected with HIV-1 in the pediatric HIV/AIDS cohort study. Hormone Research in Paediatrics. 2011;76(6):386-391. Available at http://www.ncbi.nlm.nih.gov/pubmed/22042056.
- Rasmussen LD, Mathiesen ER, Kronborg G, Pedersen C, Gerstoft J, Obel N. Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide population-based cohort study. PLoS One. 2012;7(9):e44575. Available at http://www.ncbi.nlm.nih.gov/pubmed/22984529.
- Feeney ER, Mallon PW. Insulin resistance in treated HIV infection. Best Practice & Research. Clinical Endocrinology & Metabolism. 2011;25(3):443-458. Available at http://www.ncbi.nlm.nih.gov/pubmed/21663838.
- Hazra R, Hance LF, Monteiro JP, et al. Insulin resistance and glucose and lipid concentrations in a cohort of perinatally HIV-infected Latin American children. Pediatr Infect Dis J. 2013;32(7):757-759. Available at http://www.ncbi.nlm.nih.gov/pubmed/23360832.
- Patel K, Wang J, Jacobson DL, et al. Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus. Circulation. 2014;129(11):1204-1212. Available at http://www.ncbi.nlm.nih.gov/pubmed/24366631.
- Hadigan C, Kattakuzhy S. Diabetes mellitus type 2 and abnormal glucose metabolism in the setting of human immunodeficiency virus. Endocrinology and Metabolism Clinics of North America. 2014;43(3):685-696. Available at http://www.ncbi.nlm.nih.gov/pubmed/25169561.
- Fortuny C, Deya-Martinez A, Chiappini E, Galli L, de Martino M, Noguera-Julian A. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents. Pediatr Infect Dis J. 2015;34(5 Suppl 1):S36-43. Available at http://www.ncbi.nlm.nih.gov/pubmed/25629891.
- Loomba-Albrecht LA, Bregman T, Chantry CJ. Endocrinopathies in children infected with human immunodeficiency virus. Endocrinology and Metabolism Clinics of North America. 2014;43(3):807-828. Available at http://www.ncbi.nlm.nih.gov/pubmed/25169569.
- Innes S, Abdullah KL, Haubrich R, Cotton MF, Browne SH. High prevalence of dyslipidemia and insulin resistance in HIV-infected pre-pubertal african children on antiretroviral therapy. Pediatr Infect Dis J. 2015. Available at http://www.ncbi.nlm.nih.gov/pubmed/26421804.
- American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2016;39 Suppl 1:S13-22. Available at http://www.ncbi.nlm.nih.gov/pubmed/26696675.
- Espiau M, Yeste D, Noguera-Julian A, et al. Metabolic syndrome in children and adolescents living with HIV. Pediatr Infect Dis J. 2016;35(6):e171-176. Available at http://www.ncbi.nlm.nih.gov/pubmed/26910591.
- Mirani G, Williams PL, Chernoff M, et al. Changing trends in complications and mortality rates among U.S. youth and young adults with HIV infection in the Era of Combination Antiretroviral Therapy. Clin Infect Dis. 2015;61(12):1850-1861. Available at http://www.ncbi.nlm.nih.gov/pubmed/26270680.