Synthetic approaches and application of clinically approved small-molecule Anti-HIV drugs: An update

Application of chemotherapeutic agents to inhibit the HIV replication process has brought about a significant metamorphosis in the landscape of AIDS. Substantial declines in morbidity and mortality rates have been attained, accompanied by notable decreases in healthcare resource utilization. However, treatment modalities do not uniformly inhibit HIV replication in every patient, while the emergence of drug-resistant viral strains poses a substantial obstacle to subsequent therapeutic interventions. Furthermore, chronic administration of therapy may lead to the manifestation of toxicities. These challenges necessitate the exploration of novel pharmacological agents and innovative therapeutic approaches aimed at effectively managing the persistent viral replication characteristic of chronic infection. This review examines the role of clinically approved small-molecule drugs in the treatment of HIV/AIDS, which provides an in-depth analysis of the major classes of small-molecule drugs, including nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors, entry inhibitors, and pharmacokinetic enhancers. The review mainly discusses the application, synthetic routes, and mechanisms of action of small-molecule drugs employed in the treatment of HIV, as well as their use in combination with antiretroviral therapy, presenting viewpoints on forthcoming avenues in the development of novel anti-HIV drugs.