Tenofovir

Is the first approved drug that is a nucleotide analog, namely, an acyclic nucleoside phosphonate analog of adenosine 5’-monophosphate. It is converted by cellular enzymes to the diphosphate, which is the inhibitor of HIV reverse transcriptase. Cross-resistance with other NRTIs may occur, but some AZT-resistant strains retain susceptibility to tenofovir. Tenofovir has a long half-life, allowing once-daily dosing. Most of the drug is recovered unchanged in the urine, and elimination is by filtration and active secretion. Serum creatinine must be monitored and doses adjusted in renal insuffi ciency. GI complaints are frequent and include nausea, diarrhea, and bloating Tenofovir is the only NRTI with signifi cant antiretroviral drug interactions. Tenofovir increases the concentrations of ddI to the point that ddI dosage reductions are required if the two are given together. However, these two agents are no longer recommended for combined use. Tenofovir decreases the concentrations of atazanavir such that atazanavir must be boosted with ritonavir if given with tenofovir to maintain eff ective atazanavir concentrations Tenofovir also has activity against HBV Adverse effects include GI distress, asthenia, and headache; rare cases of acute renal failure and Fanconi’s syndrome have been reported.