Metabolic and Hepatobiliary Side Effects of Antiretroviral Therapy (ART)
Section snippets
Pharmacology of ART
The abbreviation NRTI refers to either nucleoside reverse transcriptase inhibitors or nucleotide reverse transcriptase inhibitors. Both have essentially the same mechanism of action; they are analogues of native deoxynucleotides, such as thymidine, guanosine, or uridine. The only difference between these 2 classes is that nucleosides need to be phosphorylated once they enter the cell. Their structure allows them to be incorporated into the growing viral DNA strand in place of their analogous
Hepatobiliary complications
It is often difficult to determine whether hepatic injury is a direct medication side effect, drug-drug interaction, or unrelated to medications. Hepatic injury from ART may result in long-term liver damage with jaundice, cirrhosis, and fulminant hepatic failure.10 Liver toxicity in HIV-infected patients increases health care costs as a result of prolonged hospital stays from ART associated toxicity.9 Life-threatening events related to hepatic damage occur in about 2.6 per 100 person-years on
Metabolic complications
The metabolic complications associated with ARTs may indirectly increase the risk of several acute life-threatening conditions such as diabetic ketoacidosis and myocardial infarction. The treatment of these complications does not differ from the standard therapy provided for patients not infected with HIV, but physicians should recognize ART as a nontraditional risk factor for these medical diseases.
Adverse effects of ART in overdose and postexposure prophylaxis
There is limited experience with intentional overdose of ARTs, but it seems that there may be no additional risks associated with an overdose of these medications outside of the already recognized adverse effects. Seizures are reported from zidovudine (NRTI).45 In patients who are naive to these drugs it would seem extremely unlikely that metabolic complications would occur following a single acute ingestion, but many of the hepatobiliary complications have occurred after only a few doses.
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Cited by (17)
Management of Human Immunodeficiency Virus in the Emergency Department
2018, Emergency Medicine Clinics of North AmericaCitation Excerpt :Interestingly, pancreatitis has also been linked to mitochondrial toxicity of NRTIs. Stavudine and didanosine have historically been implicated most in cases of symptomatic lactic acidosis and pancreatitis.33–35 Emergent hepatobiliary side effects of ART include hepatitis and hyperbilirubinemia.
HIV and the digestive system
2018, Digestive Diseases in Sub-Saharan Africa: Changes and ChallengesNutrition Therapy for Adults with HIV on ART
2015, Health of HIV Infected People: Food, Nutrition and Lifestyle with Antiretroviral DrugsAcute pancreatitis in HIV/AIDS patients: An issue of concern
2013, Asian Pacific Journal of Tropical BiomedicineThe role of nucleoside reverse transcriptase inhibitors usage in the incidence of hyperlactatemia and lactic acidosis in HIV/AIDS patients
2012, Biomedicine and PharmacotherapyCitation Excerpt :Tissues and organs cannot function properly, and the damage becomes clinically apparent [16]. The clinical use of NRTI has been associated with adverse effects caused by mitochondrial dysfunction, such as acute pancreatitis, myopathy, peripheral neuropathy, anemia, neutropenia, hepatic toxicity and hyperlactatemia/lactic acidosis [8,12,14,17,18]. The higher rate of hyperlactatemia and lactic acidosis in our study is partially due to the relatively high rate of women in comparison with other studies.