title: [Tenofovir alafenamide fumarate - a new generation of tenofovir].
abstract: Antiretroviral therapy as a life-long treatment has to meet the criteria of maximum efficiency while maintaining the highest possible level of safety and tolerance. Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug with an excellent effect of virological suppression. However, some patients can over time develop clinically significant nephrotoxicity or bone loss. Tenofovir alafenamide fumarate (TAF) is a novel prodrug of tenofovir (TFV) that is more stable in human plasma and more efficiently penetrates into target cells than TFV. Tenofovir converted from TAF reaches plasma concentration which is 90% lower than that of TFV converted from TDF. Conversely, the active metabolite converted from TAF reaches a higher intracellular level in target cells than TFV from TDF. This allows a substantial reduction of its oral dose, decreasing the risk for renal and bone toxicity. It is even possible to reduce the dose of TAF in case it is administered concurrently with cobicistat further improving its absorption and optimizing its pharmacokinetic profile. Pharmacokinetic properties are another factor substantially influencing its safety profile. TAF is not a substrate for renal organic anion transporters and thus shows no cytotoxicity related to their expression. Based on clinical trials, a fixed-dose combination tablet (single-tablet regimen) containing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate was approved by the FDA in November 2015. This regimen showed higher efficacy, better safety profile and tolerance than TDF-based regiments. Recently, it has been approved in European Union countries.
authors.affiliation: Department of Infectious Disease, Faculty of Medicine and University Hospital, Masaryk University, Brno, Czech Republic, e-mail: svatava.snopkova@fnbrno.cz.
authors.forename: Svatava
authors.initials: S
authors.lastname: Snopková
authors.forename: Kateřina
authors.initials: K
authors.lastname: Havlíčková
authors.forename: Petr
authors.initials: P
authors.lastname: Husa
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000409:Alanine; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004338:Drug Combinations; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D000068698:Tenofovir / Q000031:analogs & derivatives
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D000068698:Tenofovir; C442442:tenofovir alafenamide; D000225:Adenine; D000409:Alanine