When HIV-1 infects a susceptible cell, the single-stranded RNA genome found in the virion is converted into double-stranded DNA.  This conversion process is carried out by the viral enzyme reverse transcriptase (RT); RT is a component of the virion.  RT has two enzymatic activities, a DNA polymerase that can copy either an RNA or a DNA template, and an RNase H that cleaves RNA if, and only if, the RNA is part of an RNA/DNA duplex.  Although there are other proteins (notably nucleocapsid) that help RT carry out its functions, RT is the only enzyme that has a direct role in the conversion of the single-stranded RNA genome into double-stranded DNA.  Not surprisingly, RT is essential for viral replication.  The polymerase of HIV-1 RT is a major target for anti-HIV-1 drugs.

There are two classes of anti-HIV-1 drugs: 1) nucleoside analogs (NRTIs), which lack the 3'OH found on normal nucleosides and act as chain terminators when incorporated into viral DNA by HIV-1 RT; and 2) nonnucleoside inhibitors (NNRTIs), which bind in a hydrophobic pocket of HIV-1 RT near the polymerase active site. 

NNRTI binding distorts the enzyme.  Both the nucleic acid and the incoming dNTP can still be bound; however, an NNRTI-inhibited enzyme cannot carry out the chemical step of the polymerization reaction.  Although both NRTI and NNRTI inhibitors can effectively inhibit the replication of wild-type HIV-1, treatment with either class of drugs selects for resistant viruses.  NNRTI-resistant and NRTI-resistant viruses have changes in the sequences encoding RT.  NNRTI resistance involves changes in amino acids that are near the NNRTI binding pocket.  In contrast, only some of the mutations that lead to NRTI resistance are in the dNTP binding pocket.  Additional information on NNRTI binding/resistance and NRTI resistance can be found at Nonnucleoside RT Inhibitors and Nucleoside RT Inhibitors, respectively.