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

Lipodystrophies and Weight Gain

Last Updated: April 14, 2020; Last Reviewed: April 14, 2020

References

See the archived version of Supplement III, February 23, 2009, Pediatric Guidelines 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. Alves Junior CAS, de Lima LRA, de Souza MC, Silva DAS. Anthropometric measures associated with fat mass estimation in children and adolescents with HIV. Appl Physiol Nutr Metab. 2019;44(5):493-498. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30286302.
  3. Kumar S, Samaras K. The impact of weight gain during HIV treatment on risk of pre-diabetes, diabetes mellitus, cardiovascular disease, and mortality. Front Endocrinol (Lausanne). 2018;9:705. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30542325.
  4. 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.
  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. J Pediatr Gastroenterol Nutr. 2014;59(4):449-454. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24709829.
  7. Nduka CU, Uthman OA, Kimani PK, Stranges S. Body fat changes in people living with HIV on antiretroviral therapy. AIDS Rev. 2016;18(4):198-211. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27438580.
  8. 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.
  9. 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.
  10. Sharma TS, Somarriba G, Arheart KL, et al. Longitudinal changes in body composition by dual-energy radiograph absorptiometry among perinatally HIV-infected and HIV-uninfected youth: increased risk of adiposity among HIV-infected female youth. Pediatr Infect Dis J. 2018;37(10):1002-1007. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29474262.
  11. de Castro JAC, de Lima LRA, Silva DAS. Accuracy of octa-polar bioelectrical impedance analysis for the assessment of total and appendicular body composition in children and adolescents with HIV: comparison with dual energy X-ray absorptiometry and air displacement plethysmography. J Hum Nutr Diet. 2018;31(2):276-285. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28799180.
  12. Hill A, Waters L, Pozniak A. Are new antiretroviral treatments increasing the risks of clinical obesity? J Virus Erad. 2019;5(1):41-43. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30800425.
  13. Taramasso L, Ricci E, Menzaghi B, et al. Weight gain: a possible side effect of all antiretrovirals. Open Forum Infect Dis. 2017;4(4):ofx239. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29255735.

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. Arrive E, Viard JP, Salanave B, et al. Metabolic risk factors in young adults infected with HIV since childhood compared with the general population. PLoS One. 2018;13(11):e0206745. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30408056.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Innes S, Harvey J, Collins IJ, Cotton MF, Judd A. Lipoatrophy/lipohypertrophy outcomes after antiretroviral therapy switch in children in the UK/Ireland. PLoS One. 2018;13(4):e0194132. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29617438.
  11. Bhagwat P, Ofotokun I, McComsey GA, et al. Changes in waist circumference in HIV-infected individuals initiating a raltegravir or protease inhibitor regimen: effects of sex and race. Open Forum Infect Dis. 2018;5(11):ofy201. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30465010.
  12. Norwood J, Turner M, Bofill C, et al. Brief Report: Weight gain in persons with HIV switched from efavirenz-based to integrase strand transfer inhibitor-based regimens. J Acquir Immune Defic Syndr. 2017;76(5):527-531. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28825943.
  13. Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis. 2019. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31100116.
  14. Gomez M, Seybold U, Roider J, Harter G, Bogner JR. A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015–2017. Infection. 2019;47(1):95-102. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30269210.
  15. Eckard AR, McComsey GA. Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2020;33(1):10-19. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31789693.

Management

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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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