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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

d4T

ddI

LPV/r

IDV

Rarely other PIs
Onset:
Weeks to months after beginning therapy

Presentation:
  • 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%
DM:
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)
Prevention:
  • Lifestyle modification
  • Avoid ZDV, d4T, ddI when possible.
Monitoring:
  • 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

References

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