Tenofovir Alafenamide: A Review of Its Use in the Treatment of HIV-1 Infection

Objective: To review the pharmacology, efficacy, safety, and place in therapy for tenofovir alafenamide (TAF). Data Sources: A search using PubMed was conducted (2004 to May 2016) using the following keywords: tenofovir alafenamide, TAF, and GS-7340. Articles were evaluated for content, and bibliographies were reviewed. Data available exclusively as abstracts from major infectious diseases and HIV conferences were also evaluated for inclusion. Study Selection and Data Extraction: Studies included were in vitro investigations; phase I, II, and III clinical trials; and pharmacokinetic and pharmacodynamic evaluations. Data Synthesis: Similar to tenofovir disoproxil fumarate (TDF), TAF is a prodrug of tenofovir but results in significantly higher intracellular tenofovir concentrations and lower serum levels. As a result, TAF is expected: to have efficacy similar to that of TDF while reducing tenofovir-associated nephrotoxicity and bone mineral density loses. Clinical trials evaluating the safety and efficacy of TAF-containing antiretroviral regimens have confirmed these expectations, consistently demonstrating similar virological suppression compared with TDF-containing regimens as well as significant improvements in markers of kidney function and bone health. Three combination products containing TAF were approved by the United States Food and Drug Administration for the management of HIV-1 infection. The first of these was a single tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF which is now a recommended regimen in clinical practice guidelines for initial treatment in antiretroviral-naive patients. Conclusions: TAF is a novel nucleotide reverse transcriptase inhibitor for the treatment of HIV-I infection that has efficacy similar to that of TDF and improved safety compared with TDF.