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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:2/12/2014; last reviewed:2/12/2014)

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Table 11f. 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 Thymidine analogue NRTIs (i.e., d4T, ddI, ZDV)

Several PIs (i.e., IDV, LPV/r; less often ATV, ATV/r, DRV/r, TPV/r)
Onset:
  • Weeks to months after beginning therapy; median of 60 days (adult data)
Presentation:
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)
Insulan Resistance:
ARV Treated Children:
  • 6%–33%
Impaired Fasting Glucose:
ARV-Treated Adults:
  • 3%–25%
ARV-Treated Children:
  • 0%–7%
Impaired Glucose Tolerance:
ARV-Treated Adults:
  • 16%–35%
ARV-Treated Children:
  • 3%–4%
DM:
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:
  • Very rare in HIV-infected children
Risk factors for Type 2 DM:
  • Lipodystrophy
  • Metabolic syndrome
  • Family history of DM
  • High BMI
  • Obesity
Prevention:
  • Lifestyle modification 

  • Although uncertain, avoiding the use of d4T, IDV may reduce risk.
Monitoring:
  • Monitor for polydipsia, polyuria, polyphagia, change in body habitus,and acanthosis nigricans.
Obtain RPG levels at:
  • Initiation of ARV therapy, and
  • 3–6 months after therapy initiation, and
  • 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 (i.e., low-fat diet, exercise, no smoking).

Consider changing from thymidine analogue NRTI (d4T or ZDV)-containing regimen.


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 standard OGTT; 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: ARV = antiretroviral; ATV = atazanavir; ATV/r = ritonavir-boosted atazanavir; d4T = stavudine; ddI = didanosine; DM = diabetes mellitus; DRV/r = ritonavir-boosted darunavir; FPG = fasting plasma glucose; IDV = indinavir; LPV/r = ritonavir-boosted lopinavir; NRTI = nucleoside reverse transcriptase inhibitor; OGTT = oral glucose tolerance test; PG = plasma glucose; PI = protease inhibitor; RPG = random plasma glucose; TPV/r = ritonavir-boosted tipranavir; ZDV = zidovudine

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