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©2000 International Medical Press 0956-3202/00/$17.00



were the first class of compounds to be utilized in anti-HIV therapy and remain an important component of current regimens of highly active antiretroviral therapy (HAART). Nucleoside analogue triphosphates are incorporated into elongating DNA chains, and cause chain termination due to a lack of a 3 ′ hydroxyl group (Arts et al., 1996; Gu et al., 1995). The efficacy of a nucleoside analogue depends on a number of factors including oral bioavailability, cellular uptake of the parent nucleoside and subsequent phospho-rylation by cellular enzymes, and the ability to compete with native nucleotide triphosphates for incorporation into newly synthesized DNA (Hao et al., 1988). However, the emergence of resistance-conferring mutations in the RT enzyme remains a major obstacle in the success of antiviral therapy. Drug-resistant variants of HIV-1 have emerged in patients receiving prolonged single-, double- and even triple-drug therapy that can include 3′-azido-3′-deoxythymidine (ZDV), 2′,3′-dideoxyinosine (ddI), 2′,3′-dideoxycytidine (ddC), and the (–) enantiomer of 2′

Year: 2016
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