The human immunodeficiency virus (HIV) is responsible for acquired immune deficiency syndrome (AIDS), one of the major pandemic diseases. Highly active antiretroviral therapy (HAART) is the standard HIV-treatment regimen that usually comprises a combination of three or more antiretroviral drugs. HIV reverse transcriptase inhibitors are the main HAART target, which involves the use of both nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, compounds affecting other aspects of HIV replication, such as virus entry and fusion or important viral enzymes, such as integrases and proteases, have also been developed. Natural compounds from different sources, like plants, microbial and marine organisms, showed promising anti-HIV activities to the point of establishing the basis for developing new drugs. Indeed, natural compounds-based therapies have the potential to become more efficient than conventional HAART, with less or no side effects. This review aims to gather and discuss the current information about the anti-HIV activity of natural and synthetic compounds, their history and mechanism of action as well as the role of plants and their bioactive compounds as a source of new anti-HIV drugs.
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