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The combination of different anti-HIV agents has become the standard of care for AIDS or HIV-infected individuals. Important progress has been made in the development of drugs for the clinical treatment of HIV infection. To date, 20 drugs have been approved for the treatment of AIDS. However, viral rebound during therapy, the emergence of HIV drug resistance and the need for long-term treatment modalities are the main causes for the failure of current antiretroviral therapy. There is still a need for the development of new drugs that are either less toxic, active against the growing number of drug-resistant HIV strains or directed to novel targets in the viral life cycle. Eleven of the approved anti-HIV drugs target the reverse transcriptase (RT). Among the so-called non-nucleoside RT inhibitors (NNRTIs) TSAO derivatives are an unusual class of compounds that exert their unique selectivity for HIV-1 through a specific interaction with the p51 subunit of HIV-1 RT. They are the only NNRTIs for which amino acids at both subunits (p66 and p51) of HIV-1 RT are needed for optimal interaction with the enzyme. Moreover, the TSAO compounds are the first non-peptide molecules that interfere with the dimerization of the enzyme.

TSAO Derivatives the First Non-Peptide Inhibitors of HIV-1 RT Dimerization