HAART and Hepatotoxicity

Abstract

Antiretroviral (ARV) drugs are given in combination to treat the human immunodeficiency virus (HIV)infection and to prolong the life expectancy of the patient. The increase in the levels of hepatotoxicity due to the use of above drugs has been the concern till date. Lactic acidosis, hepatocytes fatty infiltration and oxidative stress are the commonly associated hepatotoxic effects with the administration of nucleoside reverse transcriptase inhibitors. Non-nucleooside reverse transcriptase inhibitors such as nevirapine and efavirenz inhibit bile acid transport causing cholestasis which in turn causes apoptosis to the hepatocytes. Furthermore, hepatitis C and B virus co-infection and Tuberculus bacilli in HIV infected patients remains a vital risk factor for the development of hepatotoxicity associated with highly active antiretroviral therapy (HAART). Overwhelming evidences clearly shows that the ARV drugs mediated hepatotoxicity has been attributed due to their mitochondrial interference. Although a low grade of hepatotoxicity resolves, high levels of toxicity leads to discontinuation of the therapy. Hence, careful observation is necessary especially during and after HAART to study the drug-induced liver diseases.

The Healing Power of Plants: Herbal Compounds as Guardians against Antiretroviral and Antitubercular Drugs-Induced Hepatotoxicity

“…Chronic exposure to d4T in primates has been documented to cause mitochondrial toxicity, with significant damage to hepatocyte mitochondrial DNA observed in the livers of d4T-exposed monkeys [29]. Similar to other ARV medications, d4T disrupts mitochondrial catabolic β-oxidation of free fatty acids, resulting in the accumulation of lipid droplets in liver cells, leading to severe macrovesicular steatosis and hepatomegaly [31,32].…”

NNRTI and Liver Damage: Evidence of Their Association and the Mechanisms Involved

“…Various antiretroviral drug families have been shown to induce hepatic effects to a different degree. The reader is referred to several recent comprehensive reviews on the subjects [26][27][28]. In the case of NRTIs, moderate to severe hepatotoxicity rates have been reported for zidovudine, stavudine and didanosine while the newer drugs, emtricitabine, tenofovir, abacavir and lamivudine are associated with a significantly lower risk.…”

Protective and Ameliorative Effects of Hydroethanolic Extract of Piper nigrum (L.) Stem against Antiretroviral Therapy-Induced Hepatotoxicity and Dyslipidemia in Wistar Rats

“…As a result, liver injury has serious repercussions [ 6 ]. Liver toxicity and metabolic abnormalities like dyslipidemia are most common in HIV patients [ 1 , 7 , 8 ], especially in sub-Saharan Africa (SSA), where there are numerous factors that may enhance the risk of hepatotoxicity [ 9 , 10 ]. DILI is described as liver damage caused by any prescription or nonprescription drug, including small chemical molecules, biological agents, traditional Chinese medicines, natural medicines, health products, and dietary supplements.…”

“…Several mechanisms responsible for ART-associated liver toxicity in HIV patients have been reported [ 3 , 16 ]. These include oxidative stress, lipotoxicity, immune-mediated injury, mitochondrial toxicity, and accumulation of toxic metabolites, with mitochondrial toxicity being the most implicated [ 1 – 5 , 8 , 17 – 19 ].…”

“…Cross-sectional studies across the world report the prevalence of dyslipidemia to be statistically higher in HIV patients on ART than in ART-naive HIV patients [26][27][28][29]. Te present management of ART-induced toxicity is mostly based on monitoring of transaminase levels and the switching or discontinuation of ART [8,30]. Tese strategies compromise the benefts of ART and make patient management challenging [31].…”