An early event in the replication of HIV-1 is reverse transcription,whereby genomic RNA from the virus is convertedinto a cDNA–RNA complex, then into double-strandedDNA ready for integration into the host chromosome. Theenzyme that catalyzes this set of reactions is reverse tran-scriptase. RT actually operates twice prior to the integrationstep. Its first function is the creation of the cDNA–RNAcomplex; RT acts alone in this step. In the second step, theRNA chain is digested away by RNase H, whereas RT createsthe double-stranded unintegrated DNA.
All of the classical antiretroviral agents are 2',3'-dideoxynucleoside analogs. These compounds share a commonmechanism of action in inhibiting the RT of HIV.Because RT acts early in the viral infection sequence, inhibitorsof the enzyme block acute infection of cells but areonly weakly active in chronically infected ones. Eventhough the RT inhibitors share a common mechanism of action,their pharmacological and toxicological profiles differdramatically.
