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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

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Management of Medication Toxicity or Intolerance

Insulin Resistance, Asymptomatic Hyperglycemia, Diabetes Mellitus

Last Updated: April 27, 2017; Last Reviewed: April 27, 2017

Table 13f. AntiretroviralTherapy-Associated Adverse Effects and Management Recommendations—Insulin Resistance, Asymptomatic Hyperglycemia, Diabetes Mellitus
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

  • Asymptomatic fasting hyperglycemia (possibly in the setting of lipodystrophy), metabolic syndrome, or growth delay
  • Symptomatic DM (rare)
Insulin Resistance
ARV-Treated Children:
  • 6% to 12%
Impaired Fasting Glucose
ARV-Treated Children:
  • 0% to 7%
Impaired Glucose Tolerance
ARV-Treated Children:
  • 3% to 4%
ARV-Treated Children:
  • 0.2 per 100-person-years
Risk Factors for Type 2 DM:
  • Lipodystrophy
  • Metabolic syndrome
  • Family history of DM
  • High BMI (obesity)
  • Lifestyle modification
  • Avoid ZDV, d4T, ddI when possible.
  • Monitor for signs of DM, change in body habitus, acanthosis nigricans.
Obtain RPG Levels at:
  • Initiation of ARV therapy
  • 3–6 months after therapy initiation
  • Once a year thereafter
For RPG ≥140 mg/dL:
  • Obtain FPG performed after 8-hour fast and consider referral to endocrinologist.
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:
  • Patient meets diagnostic criteria for DM; consult endocrinologist.
FPG 100–125 mg/dL:
Impaired FPG is suggestive of insulin resistance; consult endocrinologist.

FPG <100 mg/dL:
Normal FPG, but Does Not Exclude Insulin Resistance:
  • Recheck FPG in 6–12 months.
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


  1. 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
  2. Hadigan C. Insulin resistance among HIV-infected patients: unraveling the mechanism. Clin Infect Dis. 2005;41(9):1341-1342. Available at
  3. Morse CG, Kovacs JA. Metabolic and skeletal complications of HIV infection: the price of success. JAMA. 2006;296(7):844-854. Available at
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. Feeney ER, Mallon PW. Insulin resistance in treated HIV infection. Best Practice & Research. Clinical Endocrinology & Metabolism. 2011;25(3):443-458. Available at
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2016;39 Suppl 1:S13-22. Available at
  17. 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
  18. 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

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