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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Dyslipidemia

(Last updated:2/12/2014; last reviewed:2/12/2014)

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Table 11b. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Dyslipidemia
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Dyslipidemia PIs:
  • All PIs, especially RTV-boosted PIs; lower incidence reported with DRV/r and ATV with or without ritonavir
NRTIs:
  • Especially d4T
NNRTIs:
  • EFV > NVP, RPV and ETR 
Onset:
  • As early as 2 weeks to months after beginning therapy
Presentation
PIs: 
  • ↑LDL-C, TC, and TG
NNRTIs:
  • ↑LDL-C, TC, and HDL-C
NRTIs:
  • ↑LDL-C, TC, and TG
10% to 20% in young children receiving LPV/RTV

20% to 50% of children receiving ART will have lipoprotein abnormalities.
Advanced-stage HIV disease

High-fat, high-cholesterol diet

Lack of exercise

Obesity

Hypertension

Smoking

Family history of dyslipidemia or premature CVD

Metabolic syndrome

Fat maldistribution 
Prevention
  • Low-fat diet
  • Exercise
  • No smoking
Monitoring
Adolescents and Adults:
  • Monitor 12-hour FLP, which includes TC, HDL-C, non-HDL-C, LDL-C, and TG, every 6–12 months. Obtain FLPs twice (>2 weeks—but ≤3 months—apart, average results) before initiating or changing lipid-lowering therapy.
Children (Aged ≥2 Years) Without Lipid Abnormalities or Additional Risk Factors:
  • Obtain non-fasting screening lipid profiles before initiating or changing therapy and then, if levels are stable, every 6–12 months. If TG or LDL-C is elevated, obtain fasting blood tests.
Children with Lipid Abnormalities and/or Additional Risk Factors:
  • Obtain 12-hour FLP before initiating or changing therapy and every 6 months thereafter (more often if indicated).
Children Receiving Lipid-Lowering Therapy with Statins or Fibrates:
  • Obtain 12-hour FLP, LFTs, and CK at 4 and 8 weeks, and 3 months after starting lipid therapy.
  • If minimal alterations in AST, ALT, and CK, monitor every 3–4 months in the first year and every 6 month thereafter (or as clinically indicated).
  • Repeat FLPs 4 weeks after increasing doses of antihyper-lipidemic agents.
Assessment of additional CVD risk factors should be done in all patients. HIV-infected patients are considered to be at moderate risk of CVD.a

Counsel lifestyle modification, dietary interventions (e.g., low-fat diet; low simple carbohydrate diet in case of ↑TG; exercise, smoking cessation) for adequate trial period (3–6 months).

Pharmacologic Management:
  • Dyslipidemic children aged ≥10 years with LDL-C ≥250 mg/dL or TG levels ≥500 mg/dL and all children aged <10 years who require lipid-lowering treatment should be managed by a lipid specialist. 
Statin-related toxicities include liver enzyme elevation and myopathy, and risk may be increased by drug interactions with antiretroviral treatment.b Risks must be weighed against potential benefits

Consider switching to a new ART regimen less likely to cause lipid abnormalities. 

Consider lipid-lowering therapy in consultation with a lipid specialist if 6-month trial of lifestyle modification fails.

No consensus exists as to what LDL-C should prompt treatment in children receiving ARV drugs. Drug therapy cut points recommended by NHLBI cardiovascular risk reduction guidelines for children aged ≥10 years: LDL–C ≥190 mg/dL, regardless of additional risks factors; LDL-C ≥160 mg/dL or LDL-C ≥130 mg/dL based on presence of additional risk factors and risk conditions.a

The minimal goal of therapy should be to achieve and maintain a LDL-C value below 130 mg/dL.

Initiate Drug Therapy Promptly in Patients with TG ≥500 mg/dL:
  • Statins such as pravastatin, atorvastatin, or rosuvastatin.b  Ezetimibe can be considered in addition to statins.c
Fibrates (gemfibrozil and fenofibrate) and N-3 PUFAs derived from fish oils may be used as alternative agents for adults with ↑TG but are not approved for use in children. The long-term risks of lipid abnormalities in children receiving cART are unclear. However, persistent dyslipidemia in children may lead to premature CVD.
a Refer to NHLBI guidelines at http://www.nhlbi.nih.gov/guidelines/cvd_ped/summary.htm#chap9
b The risks of new treatment-related toxicities and virologic failure that could occur with changes in therapy must be weighed against the potential risk of drug interactions and toxicities associated with the use of lipid-lowering agents.
c Statins (HMG-CoA reductase inhibitors) are contraindicated in pregnancy (potentially teratogenic) and should not be used in patients who may become pregnant. Multiple drug interactions exist between ARV drugs and statins (exception pravastatin, which is not dependent on CYP3A4 for metabolism). Pravastatin, atorvastatin, rosuvastatin (Crestor®), fluvastatin, and ezetimibe (Zetia®) are approved for use in children aged ≥10 years

Key to Acronyms: ALT = alanine transaminase; ARV = antiretroviral; AST = aspartate aminotransferase; ATV = atazanavir; cART = combination antiretroviral therapy; CK = creatine kinase; CVD = cardiovascular disease; DRV/r = darunavir/ritonavir; d4T = stavudine; EFV = efavirenz; FLP = Fasting Lipid Profile; HDL-C = high-density lipoprotein cholesterol; non-HDL-C= non-high-density lipoprotein cholesterol; LDL-C = low density lipoprotein cholesterol; LFT = liver function test; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PUFA = polyunsaturated fatty acid; RPV = rilpivirine; TC = total cholesterol; TG = triglyceride; RTV=ritonavir; ETR=etravirine

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