Twenty-six years of anti-HIV drug discovery: where do we stand and where do we go?

نویسندگان

Youcef Mehellou

Erik De Clercq

چکیده

The human immunodeficiency virus (HIV) has now been established as the causative agent of the acquired immunodeficiency syndrome (AIDS) for over 20 years. During this time an unprecedented success has been achieved in discovering anti-HIV drugs as reflected by the fact that there are now more drugs approved for the treatment of HIV than for all other viral infections taken together. The currently Food and DrugAdministration (FDA) approved anti-HIVdrugs can be divided into seven groups: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). This arsenal of drugs, which is used in combinations, has moved the prognosis of HIV patients from that of high morbidity and mortality to, for many at least, a chronic, manageable but still complex disease. However, the use of these drugs has been relatively limited by their toxicity, drug resistance development, and more worryingly, the fact that some newly HIV-infected patients carry viruses that are already resistant to the currently approvedAIDS treatments. These issues along with drug-related side effects as well as, in some cases, poor tolerability of these drugs make it apparent that new anti-HIV drugs with acceptable toxicity and resistance profiles and, more importantly, new anti-HIV agents with novel mechanisms of action are clearly needed.

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