Apr. 07, 2021

Management of Medication Toxicity or Intolerance

Hepatic Events

Table 15e. Antiretroviral Therapy–Associated Adverse Effects and Management Recommendations—Hepatic Events
Table 15e. Antiretroviral Therapy–Associated Adverse Effects and Management Recommendations—Hepatic Events



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. 2019. 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.
  10. Cai J, Osikowicz M, Sebastiani G. Clinical significance of elevated liver transaminases in HIV-infected patients. AIDS. 2019;33(8):1267-1282. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31008799.
  11. Tadesse BT, Foster BA, Kabeta A, et al. Hepatic and renal toxicity and associated factors among HIV-infected children on antiretroviral therapy: a prospective cohort study. HIV Med. 2019;20(2):147-156. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30474906.
  12. Pillaye JN, Marakalala MJ, Khumalo N, Spearman W, Ndlovu H. Mechanistic insights into antiretroviral drug-induced liver injury. Pharmacol Res Perspect. 2020;8(4):e00598. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32643320.
  13. Naidoo K, Hassan-Moosa R, Mlotshwa P, et al. High rates of drug-induced liver injury in people living with HIV coinfected with tuberculosis (TB) irrespective of antiretroviral therapy timing during antituberculosis treatment: results from the starting antiretroviral therapy at three points in TB trial. Clin Infect Dis. 2020;70(12):2675-2682. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31622456.
  14. Sudjaritruk T, Bunupuradah T, Aurpibul L, et al. Nonalcoholic fatty liver disease and hepatic fibrosis among perinatally HIV-monoinfected Asian adolescents receiving antiretroviral therapy. PLoS One. 2019;14(12):e0226375. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31856189.
  15. Gervasoni C, Cattaneo D, Filice C, Galli M, Gruppo Italiano Studio Nimi. Drug-induced liver steatosis in patients with HIV infection. Pharmacol Res. 2019;145:104267. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31077811.

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 Clin Pharmacol. 2017;73(4):463-468. Available at: https://pubmed.ncbi.nlm.nih.gov/28028587.

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: https://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: https://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.


Management of Medication Toxicity or Intolerance

Hepatic Events

Table 15e. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Hepatic Events
Table 15e. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Hepatic Events


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