Zidovudine, Lamivudine, and Abacavir

Abstract

The history of the discovery and development of zidovudine (ZDV; or 3′-azido-3′-deoxythymidine, AZT, or Retrovir™, formerly BW A509U) is fascinating not only because it was the first Food and Drug Administration (FDA)-approved agent for the treatment of HIV, but for the unprecedented speed with which this drug moved through the new-drug approval process (Table 1). In March 1987, ZDV was approved by the FDA for use in HIV-infected individuals with a previous episode of Pneumocystis carinii pneumonia (PCP) and/or a CD4 cell count of less than 200 cells/mm3. The use of ZDV in asymptomatic or symptomatic patients with CD4 cell counts greater than 500 cells/mm3 was approved in March 1990. ZDV was initially approved as a monotherapy. Subsequently, ZDV was approved for use in combination regimens with zalcitabine and lamivudine (3TC, Epivir®). Although early studies demonstrated clinical and survival benefits of ZDV alone or in combination with other nucleoside analogs, these benefits were of limited durability because of incomplete virological suppression and the emergence of resistant HIV strains. ZDV is currently approved for the treatment of HIV infection in combination regimens with potent antiretroviral agents, including HIV protease inhibitors (PIs); nonnucleoside reverse transcriptase inhibitors (NNRTIs); and potent nucleoside reverse transcriptase inhibitors (NRTIs), such as abacavir (ABC).