From adefovir to Atripla™ via tenofovir, Viread™ and Truvada™

Abstract

With the recent approvalof Atripla™ by the US FDA for the treatment of AIDS as the first triple-drug combination one-a-day pill, it would appear appropriate to review both the origin and development of this anti-HIV medicine. Atripla consists of three active ingredients, a nucleotide reverse transcriptase inhibitor (NtRTI), a nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI). The cornerstone in Atripla is the NtRTI tenofovir disoproxil fumarate (Viread™) complemented by the NRTI emtricitabine (Emtriva™) and the NNRTI efavirenz (Sustiva™). This triple-drug combination offers a number of advantages compared with the single-drug regimens, such as synergistic mechanism of action, decreased risk of drug-resistance development and reduction of toxic side effects of the individual drugs, while increasing drug compliance (based on once-daily dosing). Since the first NtRTI, adefovir, was described as an antiretroviral agent, it has taken exactly 20 years to successfully develop its combination with emtricitabine and efavirenz as the ‘combo’ pill Atripla for the treatment of AIDS.