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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Lipodystrophy, Lipohypertrophy, Lipoatrophy

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

Table 13h. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Lipodystrophy, Lipohypertrophy, Lipoatrophy
Adverse Effects
Associated ARVs Onset/
Clinical Manifestations
Estimated Frequency Risk Factors  Prevention/
Lipodystrophy (Fat Maldistribution)
General Information
See below for specific associations. Onset:
  • Trunk and limb fat initially increase within a few months of start of cART; peripheral fat wasting may not appear for 12 to 24 months after cART initiation.
Highly Variable in Adults:
  • 2% to 93%
  • 1% to 34%, perhaps more common in adolescents than pre-pubertal children
Genetic predisposition


HIV-associated inflammation

Older age

Longer duration of cART

Body habitus 
See below. Variability depends to some degree upon measures used to define lipodystrophy.
Central Lipohypertrophy
Can occur in the absence of cART, but most associated with PIs and EFV; EFV also associated with gynecomastia and breast hypertrophy Presentation:
  • Central fat accumulation with increased abdominal girth, which may include dorsocervical fat pad (buffalo hump) and/or gynecomastia in males or breast hypertrophy in females. The appearance of central lipohypertrophy is accentuated in the presence of peripheral fat wasting (lipoatrophy).
  • Up to 93%
  • Up to 27%
Obesity before initiation of therapy

Sedentary lifestyle
  • Calorically appropriate low-fat diet and exercise
  • Measure BMI
  • Body circumference and waist-hip ratio
Calorically appropriate low-fat diet and exercise, especially strength training

Smoking cessation (if applicable) to decrease future CVD risk

Data are Insufficient to Allow the Panel to Safely Recommend Use of Any of the Following Modalities in Children:
  • Recombinant
  • Human growth hormone
  • Growth hormone-releasing hormone
  • Metformin
  • Thiazolidinediones
  • Anabolic steroids
  • Liposuction

Facial/Peripheral Lipoatrophy Most associated with thymidine analogues NRTI (d4T > ZDV) Presentation:
  • Thinning of subcutaneous fat in face, buttocks, and extremities, measured as decrease in trunk/limb fat by DXA or triceps skinfold thickness. Preservation of lean body mass distinguishes lipoatrophy from HIV-associated wasting.
  • 13% to 59% (particularly in patients on d4T-containing regimens)

  • Up to 47% (particularly in patients on d4T- containing regimens)
  • Risk lower (up to 15%) in patients not treated with d4T or ZDV
d4T and ZDV

Underweight before cART
  • Avoid use of d4T and ZDV.
  • Patient self-report and physical exam are the most sensitive methods of monitoring lipoatrophy.
Switch from d4T or ZDV to other NRTIs if possible without loss of virologic control.

Data are Insufficient to Allow the Panel to Safely Recommend Use of Any of the Following Modalities in Children:
  • Injections of poly-L-lactic acid
  • Recombinant human leptin
  • Autologous fat transplantation
  • Thiazolidinediones.
Key to Acronyms: ARV = antiretroviral; BMI = body mass index; cART = combination antiretroviral therapy; CVD = cardiovascular disease; d4T = stavudine; DXA = dual energy x-ray absorptiometry; EFV = efavirenz; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; ZDV = zidovudine


See the archived version of Supplement III, February 23, 2009 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection ( for a more complete discussion and reference list.

General Reviews

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  8. Innes S, Cotton MF, Haubrich R, et al. High prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy: a cross-sectional study. BMC Pediatr. 2012;12:183. Available at
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Associated ARVs/Etiology

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  3. Haubrich RH, Riddler SA, DiRienzo AG, et al. Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment. AIDS. Jun 1 2009;23(9):1109-1118. Available at
  4. Hulgan T, Tebas P, Canter JA, et al. Hemochromatosis gene polymorphisms, mitochondrial haplogroups, and peripheral lipoatrophy during antiretroviral therapy. J Infect Dis. Mar 15 2008;197(6):858-866. Available at
  5. McComsey GA, Libutti DE, O'Riordan M, et al. Mitochondrial RNA and DNA alterations in HIV lipoatrophy are linked to antiretroviral therapy and not to HIV infection. Antivir Ther. 2008;13(5):715-722. Available at
  6. Tien PC, Benson C, Zolopa AR, Sidney S, Osmond D, Grunfeld C. The study of fat redistribution and metabolic change in HIV infection (FRAM): methods, design, and sample characteristics. Am J Epidemiol. May 1 2006;163(9):860-869. Available at
  7. Van Dyke RB, Wang L, Williams PL, Pediatric ACTGCT. Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children. J Infect Dis. Dec 1 2008;198(11):1599-1608. Available at
  8. Mulligan K, Parker RA, Komarow L, et al. Mixed patterns of changes in central and peripheral fat following initiation of antiretroviral therapy in a randomized trial. J Acquir Immune Defic Syndr. Apr 15 2006;41(5):590-597. Available at
  9. Scherzer R, Shen W, Bacchetti P, et al. Comparison of dual-energy X-ray absorptiometry and magnetic resonance imaging-measured adipose tissue depots in HIV-infected and control subjects. Am J Clin Nutr. Oct 2008;88(4):1088-1096. Available at
  10. Benn P, Sauret-Jackson V, Cartledge J, et al. Improvements in cheek volume in lipoatrophic individuals switching away from thymidine nucleoside reverse transcriptase inhibitors. HIV Med. Jul 2009;10(6):351-355. Available at
  11. Arpadi S, Shiau S, Strehlau R, Martens L, Patel F, Coovadia A, Abrams E, Kuhn L. Metabolic abnormalities and body composition of HIV-infected children on Lopinavir or Nevirapine-based antiretroviral therapy. Arch Dis Child. Apr 2013;98(4):258-264.


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  2. Carey DL, Baker D, Rogers GD, et al. A randomized, multicenter, open-label study of poly-L-lactic acid for HIV-1 facial lipoatrophy. J Acquir Immune Defic Syndr. Dec 15 2007;46(5):581-589. Available at
  3. Cavalcanti RB, Raboud J, Shen S, Kain KC, Cheung A, Walmsley S. A randomized, placebo-controlled trial of rosiglitazone for HIV-related lipoatrophy. J Infect Dis. Jun 15 2007;195(12):1754-1761. Available at
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  7. Lindegaard B, Hansen T, Hvid T, et al. The effect of strength and endurance training on insulin sensitivity and fat distribution in human immunodeficiency virus-infected patients with lipodystrophy. J Clin Endocrinol Metab. Oct 2008;93(10):3860-3869. Available at
  8. Lo J, You SM, Canavan B, et al. Low-dose physiological growth hormone in patients with HIV and abdominal fat accumulation: a randomized controlled trial. JAMA. Aug 6 2008;300(5):509-519. Available at
  9. Mulligan K, Khatami H, Schwarz JM, et al. The effects of recombinant human leptin on visceral fat, dyslipidemia, and insulin resistance in patients with human immunodeficiency virus-associated lipoatrophy and hypoleptinemia. J Clin Endocrinol Metab. Apr 2009;94(4):1137-1144. Available at
  10. Tebas P, Zhang J, Hafner R, et al. Peripheral and visceral fat changes following a treatment switch to a non-thymidine analogue or a nucleoside-sparing regimen in HIV-infected subjects with peripheral lipoatrophy: results of ACTG A5110. J Antimicrob Chemother. May 2009;63(5):998-1005. Available at
  11. Tebas P, Zhang J, Yarasheski K, et al. Switching to a protease inhibitor-containing, nucleoside-sparing regimen (lopinavir/ritonavir plus efavirenz) increases limb fat but raises serum lipid levels: results of a prospective randomized trial (AIDS clinical trial group 5125s). J Acquir Immune Defic Syndr. Jun 1 2007;45(2):193-200. Available at
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  15. Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. Sep 2010;95(9):4291-4304. Available at
  16. Ferrer E, del Rio L, Martinez E, et al. Impact of switching from lopinavir/ritonavir to atazanavir/ritonavir on body fat redistribution in virologically suppressed HIV-infected adults. AIDS Res Hum Retroviruses. Oct 2011;27(10):1061-1065. Available at
  17. Negredo E, Miro O, Rodriguez-Santiago B, et al. Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor-sparing strategy: results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA). Clin Infect Dis. Sep 15 2009;49(6):892-900. Available at
  18. Raboud JM, Diong C, Carr A, et al. A meta-analysis of six placebo-controlled trials of thiazolidinedione therapy for HIV lipoatrophy. HIV Clin Trials. Jan-Feb 2010;11(1):39-50. Available at
  19. Sheth SH, Larson RJ. The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials. BMC Infect Dis. 2010;10:183. Available at
  20. Tungsiripat M, Bejjani DE, Rizk N, et al. Rosiglitazone improves lipoatrophy in patients receiving thymidine-sparing regimens. AIDS. Jun 1 2010;24(9):1291-1298. Available at
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