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: April 16, 2019; Last Reviewed: April 16, 2019

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.
  7. Anadol E, Lust K, Boesecke C, et al. Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients. PLoS One. 2018;13(1):e0191118. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29346443.
  8. Kaspar MB, Sterling RK. Mechanisms of liver disease in patients infected with HIV. BMJ Open Gastroenterol. 2017;4(1):e000166. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29119002.
  9. Melvin AJ, Warshaw M, Compagnucci A, et al. Hepatic, renal, hematologic, and inflammatory markers in HIV-infected children on long-term suppressive antiretroviral therapy. J Pediatric Infect Dis Soc. 2017;6(3):e109-e115. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28903520.

Hepatic Events and NRTIs

  1. 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. Eur J of Clin Pharm. 2017;73(4):463-468. 

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.
  3. Bienczak A, Denti P, Cook A, et al. Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets. AIDS. 2017;31(7):905-915. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28060017.

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. 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.
  2. Rutstein RM, Samson P, Fenton T, et al. 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: https://www.ncbi.nlm.nih.gov/pubmed/25232777.
  3. 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. HIV/AIDS. 2016;8:47-65. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27022304.
  4. Cotton MF, Liberty A, Torres-Escobar I, et al. Safety and efficacy of atazanavir powder and ritonavir in HIV-1-infected infants and children from 3 months to <11 years of age: the PRINCE-2 study. Pediatr Infect Dis J. 2018;37(6):e149-e156. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29206747.
  5. European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord. Safety of darunavir and atazanavir in HIV-infected children in Europe and Thailand. Antivir Ther. 2016;21(4):353-358. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26561496.
  6. Leger P, Chirwa S, Nwogu JN, et al. Race/ethnicity difference in the pharmacogenetics of bilirubin-related atazanavir discontinuation. Pharmacogenet Genomics. 2018;28(1):1-6. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29117017.
  7. Sevinsky H, Zaru L, Wang R, et al. Pharmacokinetics and Pharmacodynamics of Atazanavir in HIV-1-Infected children treated with atazanavir powder and ritonavir: combined analysis of the PRINCE-1 and -2 studies. Pediatr Infect Dis J. 2018;37(6):e157-e165. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29206748.

HIV and Hepatitis B/C Coinfections

  1. 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.
  2. 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.
  3. European Paediatric HIVHCV Co-infection Study Group in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) in EuroCoord. Coinfection with HIV and hepatitis C virus in 229 children and young adults living in Europe. AIDS. 2017;31(1):127-135. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27898593.
  4. Neukam K, Mira JA, Collado A, et al. Liver toxicity of current antiretroviral regimens in HIV-infected patients with chronic viral hepatitis in a real life setting: The HEPAVIR SEG-HEP Cohort. PLoS One. 2016;11(2):e0148104. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26848975.
  5. Pokorska-Spiewak M, Stanska-Perka A, Popielska J, et al. Prevalence and predictors of liver disease in HIV-infected children and adolescents. Sci Rep. 2017;7(1):12309. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28951598.
  6. Scott JA, Chew KW. Treatment optimization for HIV/HCV co-infected patients. Ther Adv Infect Dis. 2017;4(1):18-36. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28357062.
  7. Sohrab SS, Suhail M, Ali A, Qadri I, Harakeh S, Azhar EI. Consequence of HIV and HCV co-infection on host immune response, persistence and current treatment options. Virusdisease. 2018;29(1):19-26. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29607354.

Nodular Regenerative Hyperplasia and Noncirrhotic Portal Hypertension

  1. 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.
  2. 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;35(8):e248-252. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27167116.
  3. 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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