title: Emtricitabine/tenofovir  in the treatment of HIV infection: current PK/PD evaluation.
abstract: BACKGROUND
  Emtricitabine/tenofovir disoproxil fumarate fixed-dose combination (FTC/TDF FDC) is the co-formulation of a nucleoside and a nucleotide, respectively. After oral administration, both drugs exhibit plasma and intracellular half-lives suitable for once-daily dosing. Within the host cells, active metabolites FTC-TP and TFV-DP act as chain terminators to the newly synthesized proviral DNA, showing synergy at enzymatic level (viral reverse transcriptase). When given in HAART combinations, FTC/TDF FDC has a remarkable effectiveness in controlling HIV replication and securing a significant CD4(+) cell recovery. If patients treated with FTC/TDF FDC fail, a lower incidence of TDF-associated K65R resistance mutation seems to develop. Furthermore, cytidine analog-associated M184V is less likely to appear with FTC than with lamivudine when both are given with TDF. FTC and TFV are not metabolized by CYP450 enzymes and are eliminated by the renal route. TFV may accumulate in tubular cells and cause a decrease in GFR and a loss of phosphates. As a onsequence, patients treated with FTC/TDF FCD may experience varied degrees of renal impairment and osteopenia/osteoporosis.
  
  
  METHODS
  This paper has focused on the PK/PD features of FTC and TDF, when given as single agent or when administered as FDC. The interpretation of efficacy/toxicity was guided by PK/PD features. The review of the available literature included also conference presentations and recent guidelines (as of May 2012).
  
  
  CONCLUSIONS
  FTC/TDF FDC is a potent and reliable component of most HAART combinations due to its maintained activity across time, as demonstrated in many trials and studies. Toxicity issues (kidney, bone) are still to be entirely elucidated and the drug-induced component well separated from patient- and HIV-related ones. However, the clinical gain associated with the use of FTC/TDF FDC is fully acknowledged by its leading position in most current treatment guidelines.
authors.affiliation: Infectious Disease Department, Foundation IRCCS Policlinico San Matteo, Piazzale Golgi, 19, 27100 Pavia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Uglietti
authors.forename: Domenico
authors.initials: D
authors.lastname: Zanaboni
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Gnarini
authors.forename: Renato
authors.initials: R
authors.lastname: Maserati
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068679:Emtricitabine; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D063065:Organophosphonates / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine