Evaluating Hepatotoxicity: A Comparative Analysis of New Generation versus Historical Antiretroviral Agents

(1) Background: Since the advent of zidovudine in 1987, antiretroviral therapy has undergone significant evolution, marked by the introduction of 34 antiretroviral drugs and 24 fixed-dose combinations. Despite these advances, hepatotoxicity remains a formidable challenge, influencing morbidity, mortality, and treatment adherence in HIV-infected patients. This study aims to compare the hepatotoxic effects of latest-generation antiretroviral medications with those of older-generation therapies, assessing their long-term impact on liver health in HIV patients. (2) Methods: This retrospective study analyzed data from 304 HIV patients treated with either latest-generation or older-generation antiretroviral drugs over four years. Patients were monitored for hepatotoxicity through liver function tests at diagnosis, six months, and one-year post-treatment initiation. (3) Results: Initial and six-month liver function tests showed no significant differences between the two groups. However, at one-year post-treatment, patients on latest-generation antiretrovirals exhibited significant improvements in ALT, AST, and ALP levels, suggesting a better safety profile regarding hepatotoxicity. Additionally, a significantly lower incidence of splenomegaly was observed in patients treated with newer medications. (4) Conclusions: The findings suggest that the latest-generation antiretroviral medications may offer a safer profile in terms of hepatotoxicity compared to older therapies, with potential benefits for long-term liver health. This study underscores the importance of continuous monitoring and further research to optimize ART strategies, ensuring improved patient outcomes and quality of life for individuals living with HIV.