Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

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Management of Medication Toxicity or Intolerance

Lipodystrophy, Lipohypertrophy, Lipoatrophy

Last Updated: May 22, 2018; Last Reviewed: May 22, 2018

References

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

General Reviews

  1. Fernandez JR, Redden DT, Pietrobelli A, Allison DB. Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr. 2004;145(4):439-444. Available at http://www.ncbi.nlm.nih.gov/pubmed/15480363.
  2. 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 http://www.ncbi.nlm.nih.gov/pubmed/20216906.
  3. 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 http://www.ncbi.nlm.nih.gov/pubmed/23176441.
  4. 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 http://www.ncbi.nlm.nih.gov/pubmed/22814353.
  5. Prendergast AJ. Complications of long-term antiretroviral therapy in HIV-infected children. Arch Dis Child. 2013;98(4):245-246. Available at http://www.ncbi.nlm.nih.gov/pubmed/23413313.
  6. 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 http://www.ncbi.nlm.nih.gov/pubmed/24709829.
  7. 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 http://www.ncbi.nlm.nih.gov/pubmed/25068287.
  8. Nduka CU, Uthman OA, Kimani PK, Stranges S. Body fat changes in people living with HIV on antiretroviral therapy. AIDS Reviews. 2016;18(4):198-211. Available at https://www.ncbi.nlm.nih.gov/pubmed/27438580.
  9. Kenny J, Doerholt K, Gibb DM, Judd A, Collaborative HIVPSSC. Who gets severe gynecomastia among HIV-infected children in the United Kingdom and Ireland? Pediatr Infect Dis J. 2017;36(3):307-310. Available at https://www.ncbi.nlm.nih.gov/pubmed/27879556.
  10. Ramteke SM, Shiau S, Foca M, et al. Patterns of growth, body composition, and lipid profiles in a South African cohort of human immunodeficiency virus-infected and uninfected children: A cross-sectional study. J Pediatric Infect Dis Soc. 2017. Available at https://www.ncbi.nlm.nih.gov/pubmed/28481997.

Associated ARVs/Etiology

  1. 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 http://www.ncbi.nlm.nih.gov/pubmed/19417580.
  2. 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 http://www.ncbi.nlm.nih.gov/pubmed/18419350.
  3. 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 http://www.ncbi.nlm.nih.gov/pubmed/18771055.
  4. 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 http://www.ncbi.nlm.nih.gov/pubmed/19000014.
  5. 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 http://www.ncbi.nlm.nih.gov/pubmed/16652032.
  6. 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 http://www.ncbi.nlm.nih.gov/pubmed/18842798.
  7. 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 http://www.ncbi.nlm.nih.gov/pubmed/19490181.
  8. 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 http://www.ncbi.nlm.nih.gov/pubmed/23220209.
  9. 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.
  10. 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 http://www.ncbi.nlm.nih.gov/pubmed/26148119.
  11. 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 http://www.ncbi.nlm.nih.gov/pubmed/25115797.
  12. McComsey GA, Moser C, Currier J, et al. Body composition changes after initiation of raltegravir or protease inhibitors: ACTG A5260s. Clin Infect Dis. 2016;62(7):853-862. Available at https://www.ncbi.nlm.nih.gov/pubmed/26797215.
  13. Moure R, Domingo P, Gallego-Escuredo JM, et al. Impact of elvitegravir on human adipocytes: Alterations in differentiation, gene expression and release of adipokines and cytokines. Antiviral Res. 2016;132:59-65. Available at https://www.ncbi.nlm.nih.gov/pubmed/27216995.
  14. Group BT. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents, and young adults (BREATHER): a randomised, open-label, non-inferiority, phase 2/3 trial. Lancet HIV. 2016;3(9):e421-e430. Available at https://www.ncbi.nlm.nih.gov/pubmed/27562743.

Management

  1. Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370. Available at http://www.ncbi.nlm.nih.gov/pubmed/18057338.
  2. Hadigan C. Peroxisome proliferator-activated receptor gamma agonists and the treatment of HIV-associated lipoatrophy: unraveling the molecular mechanism of their shortcomings. J Infect Dis. 2008;198(12):1729-1731. Available at http://www.ncbi.nlm.nih.gov/pubmed/18954262.
  3. 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. 2008;93(10):3860-3869. Available at http://www.ncbi.nlm.nih.gov/pubmed/18628529.
  4. 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. 2008;300(5):509-519. Available at http://www.ncbi.nlm.nih.gov/pubmed/18677023.
  5. 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 http://www.ncbi.nlm.nih.gov/pubmed/19299471.
  6. 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. 2010;95(9):4291-4304. Available at http://www.ncbi.nlm.nih.gov/pubmed/20554713.
  7. 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 http://www.ncbi.nlm.nih.gov/pubmed/21166602.
  8. Innes S, Harvey J, Collins I, Cotton M, Judd A. Lipoatrophy/lipohypertrophy outcomes after ART switch in children in UK/Ireland. 22nd Conference on Retroviruses and Opportunistic Infections; 2016; Boston, MA.
  9. 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 http://www.ncbi.nlm.nih.gov/pubmed/19663689.
  10. 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 http://www.ncbi.nlm.nih.gov/pubmed/20400410.
  11. 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 http://www.ncbi.nlm.nih.gov/pubmed/20573187.
  12. 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 http://www.ncbi.nlm.nih.gov/pubmed/20453626.
  13. Spoulou V, Kanaka-Gantenbein C, Bathrellou I, et al. Monitoring of lipodystrophic and metabolic abnormalities in HIV-1 infected children on antiretroviral therapy. Hormones. 2011;10(2):149-155. Available at http://www.ncbi.nlm.nih.gov/pubmed/21724540.
  14. Minami R, Yamamoto M, Takahama S, Ando H, Miyamura T, Suematsu E. Comparison of the influence of four classes of HIV antiretrovirals on adipogenic differentiation: the minimal effect of raltegravir and atazanavir. Journal of Infection and Chemotherapy. 2011;17(2):183-188. Available at http://www.ncbi.nlm.nih.gov/pubmed/20706762.
  15. Young L, Wohl DA, Hyslop WB, Lee YZ, Napravnik S, Wilkin A. Effects of raltegravir combined with tenofovir/emtricitabine on body shape, bone density, and lipids in African-Americans initiating HIV therapy. HIV Clin Trials. 2015;16(5):163-169. Available at https://www.ncbi.nlm.nih.gov/pubmed/26249671.

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