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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance


(Last updated: March 5, 2015; last reviewed: March 5, 2015)

Table 13b. 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.
  • Especially d4T
  • EFV > NVP, RPV, and ETR
  • As early as 2 weeks to months after beginning therapy
Presentation: PIs:
  • ↑LDL-C, TC, and TG
  • ↑LDL-C, TC, and HDL-C
  • ↑LDL-C, TC, and TG
10% to 20% in young children receiving LPV/RTV

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

High-fat, high-cholesterol diet

Lack of exercise




Family history of dyslipidemia or premature CVD

Metabolic syndrome

Fat maldistribution
  • Low-fat diet
  • Exercise
  • Smoking-prevention counseling
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 antihyperlipidemic 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.b

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).

If receiving d4T, it should be discontinued. If receiving PI-based ART, consider switching to a new PI-sparing ART regimen or PI-based regimen containing boosted ATV or DRV, which are less likely to cause lipid abnormalities.

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

Some experts suggest treatment in children receiving ARV drugs at cut points recommended by NHLBI cardiovascular risk reduction guidelines for children aged ≥10 years: LDL-C ≥190 mg/dL, regardless of additional risk factors; LDL-C ≥160 mg/dL or LDL-C ≥130 mg/dL based on presence of additional risk factors and risk conditions.b

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 Fasting TG ≥500 mg/dL:
Statins such as pravastatin, atorvastatin, or rosuvastatin.c Ezetimibe can be considered in addition to statins.d Statin-related toxicities include liver enzyme elevation and myopathy, and risk may be increased by drug interactions with cART, particularly PIs.c Risks must be weighed against potential benefits.

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 Given the burden of collecting fasting blood samples, some practitioners routinely measure cholesterol and triglycerides from non-fasting blood samples and follow up abnormal values with a test done in the fasted state.

b Refer to NHLBI guidelines at

c 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.

d 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 aminotransferase; ART = antiretroviral therapy; ARV = antiretroviral; AST = aspartate aminotransferase; ATV = atazanavir; cART = combination antiretroviral therapy; CK = creatine kinase; CVD = cardiovascular disease; CYP3A4 = cytochrome P450 3A4; d4T = stavudine; DRV = darunavir; DRV/r = ritonavir-boosted darunavir; EFV = efavirenz; ETR = etravirine; FLP = fasting lipid profile; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; LFT = liver function test; LPV = lopinavir; NHLBI = National Heart, Lung, and Blood Institute; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; PUFA = polyunsaturated fatty acid; RPV = rilpivirine; RTV = ritonavir; TC = total cholesterol; TG = triglyceride


  1. Belay B, Belamarich PF, Tom-Revzon C. The use of statins in pediatrics: knowledge base, limitations, and future directions. Pediatrics. 2007;119(2):370-380. Available at
  2. McComsey G, Bhumbra N, Ma JF, Rathore M, Alvarez A, First Pediatric Switch S. Impact of protease inhibitor substitution with efavirenz in HIV-infected children: results of the First Pediatric Switch Study. Pediatrics. 2003;111(3):e275-281. Available at
  3. Engler MM, Engler MB, Malloy MJ, Paul SM, Kulkarni KR, Mietus-Snyder ML. Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study). Am J Cardiol. 2005;95(7):869-871. Available at
  4. Vigano A, Aldrovandi GM, Giacomet V, et al. Improvement in dyslipidaemia after switching stavudine to tenofovir and replacing protease inhibitors with efavirenz in HIV-infected children. Antivir Ther. 2005;10(8):917-924. Available at
  5. Carter RJ, Wiener J, Abrams EJ, et al. Dyslipidemia among perinatally HIV-infected children enrolled in the PACTS-HOPE cohort, 1999-2004: a longitudinal analysis. J Acquir Immune Defic Syndr. 2006;41(4):453-460. Available at
  6. Tassiopoulos K, Williams PL, Seage GR, 3rd, et al. Association of hypercholesterolemia incidence with antiretroviral treatment, including protease inhibitors, among perinatally HIV-infected children. J Acquir Immune Defic Syndr. 2008;47(5):607-614. Available at
  7. 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
  8. 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
  9. Rhoads MP, Lanigan J, Smith CJ, Lyall EG. Effect of specific ART drugs on lipid changes and the need for lipid management in children with HIV. J Acquir Immune Defic Syndr. 2011;57(5):404-412. Available at
  10. Jacobson DL, Williams P, Tassiopoulos K, Melvin A, Hazra R, Farley J. Clinical management and follow-up of hypercholesterolemia among perinatally HIV-infected children enrolled in the PACTG 219C study. J Acquir Immune Defic Syndr. 2011;57(5):413-420. Available at
  11. O'Gorman CS, O'Neill MB, Conwell LS. Considering statins for cholesterol-reduction in children if lifestyle and diet changes do not improve their health: a review of the risks and benefits. Vasc Health Risk Manag. 2011;7:1-14. Available at
  12. Estrada V, Portilla J. Dyslipidemia related to antiretroviral therapy. AIDS Rev. 2011;13(1):49-56. Available at
  13. Feeney ER, Mallon PW. HIV and HAART-Associated Dyslipidemia. Open Cardiovasc Med J. 2011;5:49-63. Available at
  14. Dube MP, Cadden JJ. Lipid metabolism in treated HIV Infection. Best Pract Res Clin Endocrinol Metab. 2011;25(3):429-442. Available at
  15. Singh S, Willig JH, Mugavero MJ, et al. Comparative Effectiveness and Toxicity of Statins Among HIV-Infected Patients. Clin Infect Dis. 2011;52(3):387-395. Available at
  16. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. The Report of the Expert Panel. 2011. Available at
  17. FDA. FDA Drug Safety Communication: Interactions between certain HIV or hepatitis C drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury. 2012. Available at
  18. Langat A, Benki-Nugent S, Wamalwa D, et al. Lipid changes in Kenyan HIV-1-infected infants initiating highly active antiretroviral therapy by 1 year of age. Pediatr Infect Dis J. 2013;32(7):e298-304. Available at
  19. Casado JL, de Los Santos I, Del Palacio M, et al. Lipid-lowering effect and efficacy after switching to etravirine in HIV-infected patients with intolerance to suppressive HAART. HIV Clin Trials. 2013;14(1):1-9. Available at
  20. Calza L, Manfredi R, Colangeli V, et al. Two-year treatment with rosuvastatin reduces carotid intima-media thickness in HIV type 1-infected patients receiving highly active antiretroviral therapy with asymptomatic atherosclerosis and moderate cardiovascular risk. AIDS Res Hum Retroviruses. 2013;29(3):547-556. Available at
  21. Lazzaretti RK, Kuhmmer R, Sprinz E, Polanczyk CA, Ribeiro JP. Dietary intervention prevents dyslipidemia associated with highly active antiretroviral therapy in human immunodeficiency virus type 1-infected individuals: a randomized trial. J Am Col Cardiol. 2012;59(11):979-988. Available at
  22. Peters BS, Wierzbicki AS, Moyle G, Nair D, Brockmeyer N. The effect of a 12-week course of omega-3 polyunsaturated fatty acids on lipid parameters in hypertriglyceridemic adult HIV-infected patients undergoing HAART: a randomized, placebo-controlled pilot trial. Clin Ther. 2012;34(1):67-76. Available at
  23. Oliveira JM, Rondo PH. Omega-3 fatty acids and hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: systematic review and meta-analysis. HIV Clin Trials. 2011;12(5):268-274. Available at
  24. Strehlau R, Coovadia A, Abrams EJ, et al. Lipid profiles in young HIV-infected children initiating and changing antiretroviral therapy. J Acquir Immune Defic Syndr. 2012;60(4):369-376. Available at
  25. Hazra R, Cohen RA, Gonin R, et al. Lipid levels in the second year of life among HIV-infected and HIV-exposed uninfected Latin American children. AIDS. 2012;26(2):235-240. Available at
  26. Arpadi S, Shiau S, Strehlau R, et al. Metabolic abnormalities and body composition of HIV-infected children on Lopinavir or Nevirapine-based antiretroviral therapy. Arch Dis Child. 2013;98(4):258-264. Available at
  27. Calvo M, Martinez E. Update on metabolic issues in HIV patients. Curr Opin HIV AIDS. 2014;9(4):332-339. Available at
  28. Barlow-Mosha L, Eckard AR, McComsey GA, Musoke PM. Metabolic complications and treatment of perinatally HIV-infected children and adolescents. J Int AIDS Soc. 2013;16:18600. Available at

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