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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: March 1, 2016; last reviewed: March 1, 2016)

Table 12f. Antiretroviral Therapy-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 Several NRTIs (e.g., d4T, ZDV, ddI)

Several PIs (e.g., LPV/r; less often ATV, ATV/r, DRV/r, NFV, TPV/r)
  • Weeks to months after beginning therapy; median of 60 days (adult data).
Most Commonly:
  • Asymptomatic fasting hyperglycemia (possibly in the setting of lipodystrophy), metabolic syndrome, or growth delay
Also Possible:
  • Frank DM (i.e., polyuria, polydipsia, polyphagia, fatigue, hyperglycemia)
Insulin Resistance
ARV-Treated Adults and Children:
  • 6% to 33%
Impaired Fasting Glucose
ARV-Treated Adults:
  • 3% to 25%
ARV-Treated Children:
  • 0% to 7%
Impaired Glucose Tolerance
ARV-Treated Adults:
  • 16% to 35%
ARV-Treated Children:
  • 3% to 4%
ARV-Treated Adults:
  • 0.6–4.7 per 100 person-years (2- to 4-fold greater than that for HIV-uninfected adults)
ARV-Treated Children:
  • Rare in HIV-infected children
Risk Factors For Type 2 DM:
  • Lipodystrophy
  • Metabolic syndrome
  • Family history of DM
  • High BMI (obesity)
  • Lifestyle modification
  • Although uncertain, avoiding the use of d4T may reduce risk.
  • Monitor for polydipsia, polyuria, polyphagia, change in body habitus, and 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, trans fat, and refined sugars; increased physical activity; cessation of smoking); consider consultation with dietician.

Change NRTI (e.g., from d4T, ZDV, or ddI to 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 75g-OGTT (or if <43 kg, 1.75 g/kg of glucose up to a maximum of 75g); 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; ATV = atazanavir; ATV/r = ritonavir-boosted atazanavir; BMI = body mass index; d4T = stavudine; ddI = didanosine; dL = deciliter; DM = diabetes mellitus; DRV/r = ritonavir-boosted darunavir; FPG = fasting plasma glucose; HgbA1c = glycosylated hemoglobin; LPV/r = ritonavir-boosted lopinavir; NFV = nelfinavir; NRTI = nucleoside reverse transcriptase inhibitor; OGTT = oral glucose tolerance test; PG = plasma glucose; PI = protease inhibitor; RPG = random plasma glucose; TDF = tenofovir disoproxil fumarate; TPV/r = ritonavir-boosted tipranavir; ZDV = zidovudine


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