Preclinical and clinical development of the anti-HIV, anti-HBV oxathiolane nucleoside analog emtricitabine

Three classes of drugs are available to treat patients infected with human immunodeficiency virus (HIV) : the nucleoside reverse transcriptase inhibitors (NRTI), the nonnucleoside reverse transcriptase inhibitors (NNRTI), and the protease inhibitors (PI). Emtricitabine represents one of the most potent anti-HIV agents identified to date, producing two log(10) drop in viral load as monotherapy at a 200 mg qd dose as the affected individual became susceptible to opportunistic infections and specific immune deficiency resulting from the depletion of CD4(+) lymphocytes. The clinical profile of emtricitabine discussed in this chapter demonstrated (1) a plasma half-life of 8-10 hours with linear kinetics, (2) an intracellular emtricitabine 5’-triphosphate half-life greater than 39 hours that supports daily dosing, (3) no significant drug–drug interactions that limits the use of emtricitabine in combination therapy, (4) comparable safety and efficacy to lamivudine, and (5) low incidence of Ml84V mutations. This important observation suggests that emtricitabine can increase the durability of oxathiolane nucleoside analog-containing drug regimens. Hepatitis B virus (HBV) constitutes a major worldwide health threat, as the clinical development program is just entering the pivotal phase. Emtricitabine can be an extremely important drug for the treatment of patients coinfected with HIV and HBV.