Antiretrovirals and mechanisms of action

Thesis Abstract

Abstract
Antiretroviral therapy (ART) is the cornerstone of treatment for HIV infection and has significantly improved the prognosis and quality of life for individuals living with HIV. The mechanisms of action of antiretrovirals are diverse and target different stages of the HIV life cycle. Nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit the reverse transcriptase enzyme, preventing the conversion of viral RNA into DNA. Protease inhibitors (PIs) block the activity of the protease enzyme, which is essential for the cleavage of viral polyproteins into functional proteins. Integrase strand transfer inhibitors (INSTIs) target the integrase enzyme, which is responsible for integrating the viral DNA into the host cell genome. Entry inhibitors prevent HIV from entering the host cell by blocking the binding of the virus to the CD4 receptor or the co-receptors on the cell surface. In addition to these mechanisms, antiretrovirals can also exert their effects through pharmacokinetic properties such as bioavailability, metabolism, and drug interactions. Drug resistance is a significant concern in the management of HIV infection, and the development of resistance mutations can limit the effectiveness of antiretroviral therapy. Combination therapy, which involves the use of multiple antiretrovirals with different mechanisms of action, is employed to reduce the risk of resistance and improve treatment outcomes. Beyond their direct antiviral effects, antiretrovirals have been shown to have immunomodulatory properties that can help restore immune function in individuals with HIV infection. By suppressing viral replication and reducing the viral load, antiretrovirals can decrease the immune activation and inflammation that contribute to HIV-associated comorbidities. Early initiation of ART is recommended to achieve viral suppression and immune reconstitution, which can prevent disease progression and reduce the risk of transmission to others. Despite the success of antiretroviral therapy in controlling HIV infection, challenges remain in ensuring universal access to treatment, addressing medication adherence, managing drug toxicities, and developing new antiretrovirals with improved efficacy and safety profiles. Ongoing research efforts focus on novel drug targets, long-acting formulations, and strategies to cure HIV infection. Overall, understanding the mechanisms of action of antiretrovirals is essential for optimizing treatment regimens and improving outcomes for individuals living with HIV.