Antiretroviral agents

In 1987, zidovudine became the first approved agent in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Almost 30 years later, more than 26 additional agents in six drug classes have been approved. These include nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), a fusion inhibitor (entry inhibitor), a chemokine coreceptor antagonist (entry inhibitor), integrase strand transfer inhibitors (Table 1), and pharmacokinetic enhancers. This success is the result of a prodigious effort to dissect the virus’ replication cycle and the virion’s interaction with its CD4 target cells to identify promising drug targets. It also illustrates the interdependency of the drug development process, knowledge of disease pathogenesis, and use of sensitive therapeutic monitoring tools like plasma HIV-1 RNA levels and drug resistance testing.