ZALCITABINE (DDC) BOOSTED LAMIVUDINE (3TC) COMPOSITIONS FOR ANTIRETROVIRAL THERAPY

摘要

Boosted cytidine analogue reverse transcriptase inhibitor antiretroviralcompound is a new therapeutic anti HIV option, in combination with anotherdrug such as a NRTI or a protease inhibitor. It's heightened and sustainedantiretroviral potency is due to the increased intracellular level of 3TCtriphosphate, the active form of 3TC. This effect is obtained by combining3TC, in usual doses, with a reduced dose of ddC, in the same pharmaceuticalformulation. The product could be administered twice or even once daily, whichis convenient, and does not increase the pill burden for the patient. Thereduced ddC dosage prevents the occurrence of ddC related side effects. Othercytidine derivatives (racemic or negative enantiomers) could have the sameeffects as ddC and could probably be combined with 3TC, and have the sameeffect. On the other hand, low dose ddC may also increase the intracellularlevels of other cytidine derivatives as it does for 3TC. Boosted cytidineanalogue reverse transcriptase inhibitor antiretroviral compound could also beformulated in combination with another drug such as another NRTI (e.g.abacavir) or any protease inhibitor in the same capsule or tablet. Thisapproach offers a dual anti-HIV therapy that is as efficacious as the routinetriple therapy. In this way the HIV treatment cost could be significantlyreduced which is imperative for resource-poor settings. This new formulationis convenient and well tolerated with no additional toxicity than that of thecombining drug (NRTI or protease inhibitor) and 3TC. Moreover, this willenable a larger number of patients to benefit from the already known 3TCeffects. It will also increase the 3TC effects in those organs or HIVsanctuaries with usually reduced 3TC concentrations or activity. It could beindicated in both the initial as well as in salvage HIV therapy. It could alsobe used for therapy optimization or simplification. Moreover, in combinationwith another NRTI such as abacavir, or even alone, it could be beneficial forreducing the HIV harm in resource-poor settings.