Efavirenz is a non-nucleoside reverse transcriptase (RT) inhibitor of HIV-1. Efavirenz activity is mediated predominantly by noncompetitive inhibition of HIV-1 reverse transcriptase. HIV-2 RT and human cellular DNA polymerases alpha, beta, gamma, and delta are not inhibited by efavirenz.
Tenofovir disoproxil fumarate is the fumarate salt of the prodrug tenofovir disoproxil. Tenofovir disoproxil is absorbed and converted to the active substance tenofovir, which is a nucleoside monophosphate (nucleotide) analogue. Tenofovir is then converted to the active metabolite, tenofovir diphosphate, an obligate chain terminator, by constitutively expressed cellular enzymes. Tenofovir diphosphate has an intracellular half-life of 10 hours in activated and 50 hours in resting peripheral blood mononuclear cells (PBMCs). Tenofovir diphosphate inhibits HIV-1 reverse transcriptase and the HBV polymerase by direct binding competition with the natural deoxyribonucleotide substrate and, after incorporation into DNA, by DNA chain termination. Tenofovir diphosphate is a weak inhibitor of cellular polymerases alpha, beta, and gamma. At concentrations of up to 300 umol/l, tenofovir has also shown no effect on the synthesis of mitochondrial DNA or the production of lactic acid in in vitro assays.