IA Nucleoside agents

These substances are analogues of thy-mine (azidothymidine, stavudine), adenine (didanosine), cytosine (lami-vudine, zalcitabine), and guanine (car-bovir, a metabolite of abacavir). They have in common an abnormal sugar moiety. Like the natural nucleosides, they undergo triphosphorylation, giving rise to nucleotides that both inhibit reverse transcriptase and cause strand breakage following incorporation into viral DNA.

The nucleoside inhibitors differ in terms of l) their ability to decrease circulating HIV load; 2) their pharmacokinetic properties (half life ^ dosing interval ^ compliance; organ distribution ^ passage through blood-brainbar-

rier); 3) the type of resistance-inducing mutations of the viral genome and the rate at which resistance develops; and 4) their adverse effects (bone marrow depression, neuropathy, pancreatitis).

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