transcriptase and cellular DNA polymerases in the sorts of DNA precursors (nucleosides) that they can utilize have been exploited to develop drugs that are selectively toxic to HIV-1.

Azidothymidine (AZT) is an example of a nucleoside analog DNA precursor that can serve as a reverse transcriptase "suicide inhibitor," because AZT incorporation into viral DNA prevents later steps in viral replication. However, the effectiveness of these sorts of drugs is limited by several factors. AZT is occasionally incorporated into cellular DNA, which contributes to the toxicity some patients experience when treated with reverse tran-scriptase inhibitors. Additionally, reverse transcriptase inhibitor resistance often develops during antiretroviral therapy. This resistance results from reverse transcriptase's high error rate, which generates a remarkable amount of genetic variation within HIV populations. If some viral genetic variants are less sensitive to antivirals than other variants, the resistant mutants will replicate during antiviral therapy. Despite these complications, reverse tran-scriptase inhibitors remain important components of the combined antiviral regimen that has dramatically lengthened the lives of many HIV-infected patients since the mid-1990s.

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