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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

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Management of Medication Toxicity or Intolerance

Lipodystrophy, Lipohypertrophy, Lipoatrophy

Last Updated: March 1, 2016; Last Reviewed: March 1, 2016

Table 12h. 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 ART; peripheral fat wasting may not appear for 12 to 24 months after ART initiation.
Varies greatly depending upon measure and comparator group

Highly Variable in Adults:
  • Up to 93%
  • Up to 34%, perhaps more common in adolescents than prepubertal children
Genetic predisposition


HIV-associated inflammation

Older age

Longer duration of ART

Body habitus
See below. See below

Although more typically associated with certain ARVs (e.g., d4T), a regimen review with consideration of changing the regimen should be considered, whenever present
Central Lipohypertrophy
Can occur in the absence of ART, but most associated with PIs and EFV. 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, particularly with EFV. 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
  • BMI measurement
  • Body circumference and waist-hip ratio
Calorically appropriate healthy diet low in saturated fats and simple carbohydrates, and exercise, especially strength training

Smoking cessation (if applicable) to decrease future CVD risk

Consider switching from PIs and EFV to an INSTI

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 analogue NRTIs (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.
Up 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.
Underweight before ART Prevention:
  • Avoid use of d4T and ZDV.
  • Patient self-report and physical exam are the most sensitive methods of monitoring lipoatrophy.
Replace d4T (not widely used and recommended only in special circumstances) or ZDV with 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: ART = antiretroviral therapy; ARV = antiretroviral; BMI = body mass index; 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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  4. Phillips DR, Hay P. Current perspectives on the management and prevention of antiretroviral-associated lipoatrophy. J Antimicrob Chemother. 2008;62(5):866-871. Available at
  5. Moyle G, Moutschen M, Martinez E, et al. Epidemiology, assessment, and management of excess abdominal fat in persons with HIV infection. AIDS reviews. 2010;12(1):3-14. Available at
  6. Dzwonek A, Clapson M, Withey S, Bates A, Novelli V. Severe gynecomastia in an African boy with perinatally acquired human immunodeficiency virus infection receiving highly active antiretroviral therapy. Pediatr Infect Dis J. 2006;25(2):183-184. Available at
  7. 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
  8. Piloya T, Bakeera-Kitaka S, Kekitiinwa A, Kamya MR. Lipodystrophy among HIV-infected children and adolescents on highly active antiretroviral therapy in Uganda: a cross sectional study. J Int AIDS Soc. 2012;15(2):17427. Available at
  9. Prendergast AJ. Complications of long-term antiretroviral therapy in HIV-infected children. Arch Dis Child. 2013;98(4):245-246. Available at
  10. Arbeitman LE, O'Brien RC, Somarriba G, et al. Body mass index and waist circumference of HIV-infected youth in a Miami cohort: comparison to local and national cohorts. Journal of Pediatric Gastroenterology and Nutrition. 2014;59(4):449-454. Available at
  11. Bwakura-Dangarembizi M, Musiime V, Szubert AJ, et al. Prevalence of lipodystrophy and metabolic abnormalities in HIV-infected African children after 3 years on first-line antiretroviral therapy. Pediatr Infect Dis J. 2015;34(2):e23-31. Available at

Associated ARVs/Etiology

  1. Dube MP, Komarow L, Mulligan K, et al. Long-term body fat outcomes in antiretroviral-naive participants randomized to nelfinavir or efavirenz or both plus dual nucleosides. Dual X-ray absorptiometry results from A5005s, a substudy of Adult Clinical Trials Group 384. J Acquir Immune Defic Syndr. 2007;45(5):508-514. Available at
  2. 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. 2009;23(9):1109-1118. Available at
  3. Hulgan T, Tebas P, Canter JA, et al. Hemochromatosis gene polymorphisms, mitochondrial haplogroups, and peripheral lipoatrophy during antiretroviral therapy. J Infect Dis. 2008;197(6):858-866. Available at
  4. 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
  5. 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. American journal of epidemiology. 2006;163(9):860-869. Available at
  6. 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. 2008;198(11):1599-1608. Available at
  7. 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. 2006;41(5):590-597. Available at
  8. 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. The American journal of clinical nutrition. 2008;88(4):1088-1096. Available at
  9. 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. 2009;10(6):351-355. Available at
  10. 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
  11. Foca M, Wang L, Ramteke R, et al. Changes in mitochondrial enzyme function as a predictor of lipodystrophy. Presented at: 7th International AIDS Society. 2015. Vancouver, Canada.
  12. Cohen S, Innes S, Geelen SP, et al. Long-term changes of subcutaneous fat mass in HIV-infected children on antiretroviral therapy: a retrospective analysis of longitudinal data from two pediatric HIV-cohorts. PLoS One. 2015;10(7):e0120927. Available at
  13. Dos Reis LC, de Carvalho Rondo PH, de Sousa Marques HH, Jose Segri N. Anthropometry and body composition of vertically HIV-infected children and adolescents under therapy with and without protease inhibitors. Public Health Nutr. 2015;18(7):1255-1261. Available at


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  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. The Journal of clinical endocrinology and metabolism. 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. 2009;63(5):998-1005. 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. The Journal of clinical endocrinology and metabolism. 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. 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. 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. 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. 2010;24(9):1291-1298. Available at
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