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

Hepatic Events

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

References

General Reviews

  1. Aurpibul L, Bunupuradah T, Sophan S, et al. Prevalence and incidence of liver dysfunction and assessment of biomarkers of liver disease in HIV-infected Asian children. Pediatr Infect Dis J. 2015;34(6):e153-158. Available at https://www.ncbi.nlm.nih.gov/pubmed/25970117.
  2. Huntington S, Thorne C, Newell ML, et al. Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy. AIDS. 2015;29(7):801-809. Available at https://www.ncbi.nlm.nih.gov/pubmed/25710412.
  3. Kovari H, Sabin CA, Ledergerber B, et al. Antiretroviral drugs and risk of chronic alanine aminotransferase elevation in human immunodeficiency virus (HIV)-monoinfected persons: the data collection on Adverse Events of Anti-HIV Drugs Study. Open Forum Infect Dis. 2016;3(1):ofw009. Available at https://www.ncbi.nlm.nih.gov/pubmed/26925429.
  4. Navarro VJ, Khan I, Bjornsson E, Seeff LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1):363-373. Available at https://www.ncbi.nlm.nih.gov/pubmed/27677775.
  5. Sonderup MW, Wainwright HC. Human immunodeficiency virus infection, antiretroviral therapy, and liver pathology. Gastroenterol Clin North Am. 2017;46(2):327-343. Available at https://www.ncbi.nlm.nih.gov/pubmed/28506368.
  6. The National Institute of Diabetes and Digestive and Kidney Diseases. Clinical and Research Information on Drug-Induced Liver Injury. 2017. Available at https://livertox.nlm.nih.gov.

Hepatic Events and NRTIs

  1. 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.
  2. Logan S, Rodger A, Maynard-Smith L, et al. Prevalence of significant liver disease in human immunodeficiency virus-infected patients exposed to Didanosine: A cross sectional study. World J Hepatol. 2016;8(36):1623-1628. Available at https://www.ncbi.nlm.nih.gov/pubmed/28083085.

Hepatic Events and NNRTIs

  1. Phillips E, Bartlett JA, Sanne I, et al. Associations between HLA-DRB1*0102, HLA-B*5801, and hepatotoxicity during initiation of nevirapine-containing regimens in South Africa. J Acquir Immune Defic Syndr. 2013;62(2):e55-57. Available at http://www.ncbi.nlm.nih.gov/pubmed/23328091.
  2. Sonderup MW, Maughan D, Gogela N, et al. Identification of a novel and severe pattern of efavirenz drug-induced liver injury in South Africa. AIDS. 2016;30(9):1483-1485. Available at https://www.ncbi.nlm.nih.gov/pubmed/26959511.

Hepatic Events and NRTIs plus NNRTIs

  1. Wu PY, Cheng CY, Liu CE, et al. Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naive HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan. PLoS One. 2017;12(2):e0171596. Available at https://www.ncbi.nlm.nih.gov/pubmed/28222098.

Hepatic Events and PIs including Indirect Hyperbilirubinemia

  1. McDonald C, Uy J, Hu W, et al. Clinical significance of hyperbilirubinemia among HIV-1-infected patients treated with atazanavir/ritonavir through 96 weeks in the CASTLE study. AIDS Patient Care STDS. 2012;26(5):259-264. Available at http://www.ncbi.nlm.nih.gov/pubmed/22404426.
  2. Strehlau R, Donati AP, Arce PM, et al. PRINCE-1: safety and efficacy of atazanavir powder and ritonavir liquid in HIV-1-infected antiretroviral-naive and -experienced infants and children aged >/=3 months to <6 years. J Int AIDS Soc. 2015;18:19467. Available at http://www.ncbi.nlm.nih.gov/pubmed/26066346.
  3. Rutstein RM, Samson P, Fenton T, Fletcher CV, Kiser JJ, Mofenson LM, et al. for the PACTG 1020A Study Team. Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children, and adolescents: The Pediatric AIDS Clinical Trials Group Protocol 1020A. Pediatr Infect Dis J. 2015;34:162-167. Available at
  4. Crutchley RD, Guduru RC, Cheng AM. Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection. Hi/Aids. 2016;8:47-65. Available at https://www.ncbi.nlm.nih.gov/pubmed/27022304.
  5. The European Pregnancy and Paediatric HIV Cohort Collaboration, (EPPICC) study group in EuroCoord. Safety of zidovudine/lamivudine scored tablets in children with HIV infection in Europe and Thailand. European Journal of Clinical Pharmacology. 2017;73(4):463-468.

HIV and Hepatitis B/C Coinfections

  1. Kovari H, Ledergerber B, Battegay M, et al. Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis b or c virus co-infection. Clin Infect Dis. 2010;50(4):502-511. Available at http://www.ncbi.nlm.nih.gov/pubmed/20085465.
  2. Gowda C, Newcomb CW, Liu Q, et al. Risk of acute liver injury with antiretroviral therapy by viral hepatitis status. Open Forum Infect Dis. 2017;4(2):ofx012. Available at https://www.ncbi.nlm.nih.gov/pubmed/28470014.
  3. Phung BC, Sogni P, Launay O. Hepatitis B and human immunodeficiency virus co-infection. World J Gastroenterol. 2014;20(46):17360-17367. Available at https://www.ncbi.nlm.nih.gov/pubmed/25516647.

Nodular Regenerative Hyperplasia and Noncirrhotic Portal Hypertension

  1. Cotte L, Benet T, Billioud C, et al. The role of nucleoside and nucleotide analogues in nodular regenerative hyperplasia in HIV-infected patients: a case control study. J Hepatol. 2011;54(3):489-496. Available at http://www.ncbi.nlm.nih.gov/pubmed/21056493.
  2. Kovari H, Ledergerber B, Peter U, et al. Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study. Clin Infect Dis. 2009;49(4):626-635. Available at http://www.ncbi.nlm.nih.gov/pubmed/19589079.
  3. Schouten JN, Van der Ende ME, Koeter T, et al. Risk factors and outcome of HIV-associated idiopathic noncirrhotic portal hypertension. Aliment Pharmacol Ther. 2012;36(9):875-885. Available at http://www.ncbi.nlm.nih.gov/pubmed/22971050.
  4. Vispo E, Morello J, Rodriguez-Novoa S, Soriano V. Noncirrhotic portal hypertension in HIV infection. Curr Opin Infect Dis. 2011;24(1):12-18. Available at http://www.ncbi.nlm.nih.gov/pubmed/21157331.
  5. Parikh ND, Martel-Laferriere V, Kushner T, et al. Clinical factors that predict noncirrhotic portal hypertension in HIV-infected patients: a proposed diagnostic algorithm. J Infect Dis. 2014;209(5):734-738. Available at https://www.ncbi.nlm.nih.gov/pubmed/23911709.
  6. Scherpbier HJ, Terpstra V, Pajkrt D, et al. Noncirrhotic portal hypertension in perinatally HIV-infected adolescents treated with didanosine-containing antiretroviral regimens in childhood. Pediatr Infect Dis J. 2016. Available at http://www.ncbi.nlm.nih.gov/pubmed/27167116.
  7. Sood A, Castrejon M, Saab S. Human immunodeficiency virus and nodular regenerative hyperplasia of liver: A systematic review. World J Hepatol. 2014;6(1):55-63. Available at https://www.ncbi.nlm.nih.gov/pubmed/24653794.

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