HIV-1 reverse transcriptase (RT) has two associated activities, DNA poly-merase and RNase H, both essential for viral replication and validated drug targets. Although all RT inhibitors approved for therapy target DNA poly-merase activity, the search for new RT inhibitors that target the RNase H function and are possibly active on RTs resistant to the known non-nucleoside inhibitors (NNRTI) is a viable approach for anti-HIV drug development.