Development of novel nucleoside analogues for use against drug resistant strains of HIV-1

Nucleoside analogue inhibitors of the reverse transcriptase (RT) enzyme of HIV-1 were the first class of compounds to be used in anti-HIV-1 therapy and are a cornerstone in highly active antiretroviral therapy. Despite the number of inhibitors of HIV-1 RT available for clinical use at the present time and the effectiveness of these compounds in combination regimens, long-term exposure of patients to these drugs often results in the development of viral resistance or long-term toxicity. For this reason, efforts to identify new agents with activity against drug-resistant strains of HIV-1 and with a toxicity profile that allows for individual patient tolerance of the drugs are still warranted.