Abstract
Due to the improved effectiveness and safety of combined antiretroviral therapy, human immunodeficiency virus (HIV) infection has become a manageable, chronic condition rather than a mortal disease. However, HIV patients are at increased risk of experiencing non-AIDS-defining illnesses, with liver-related injury standing out as one of the leading causes of death among these patients. In addition to more HIV-specific processes, such as antiretroviral drug-related toxicity and direct injury to the liver by the virus itself, its pathogenesis is related to conditions that are also common in the general population, such as alcoholic and non-alcoholic fatty liver disease, viral hepatitis, and ageing. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of combined anti-HIV treatment due to their unique antiviral activity, high specificity, and acceptable toxicity. While first-generation NNRTIs (nevirapine and efavirenz) have been related largely to liver toxicity, those belonging to the second generation (etravirine, rilpivirine and doravirine) seem to be generally safe for the liver. Indeed, there is preclinical evidence of rilpivirine being hepatoprotective in different models of liver injury, independently of the presence of HIV. The present study aims to review the mechanisms by which currently available anti-HIV drugs belonging to the NNRTI family may participate in the development of liver disease.
Highlights
One of the greatest public health achievements of the past two decades was the advent of combined antiretroviral therapy, which has dramatically diminished the incidence of opportunistic infections and the overall morbidity and mortality among patients with human immunodeficiency virus (HIV) infection
A review of the literature clearly shows that first-generation nucleoside reverse transcriptase inhibitors (NNRTIs) exert significant hepatotoxicity, unlike their second-generation counterparts, which seem to be safe for the liver, even in patients coinfected with hepatitis viruses
The same study reported evidence of mild, delayed-onset liver injury in C57BL/6 mice exposed to NVP for 3 weeks (950 mg/kg/day in standard chow diet), which presented as hepatocyte death in some lobular areas, while in some animals there was only a small increase in ALT that resolved itself despite continued treatment
Summary
One of the greatest public health achievements of the past two decades was the advent of combined antiretroviral therapy (cART), which has dramatically diminished the incidence of opportunistic infections and the overall morbidity and mortality among patients with human immunodeficiency virus (HIV) infection. Despite these positive outcomes, HIV patients are at greater risk of developing non-AIDS conditions, with chronic liver disease (CLD) being among the most prominent [1,2].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
