title: Long-Term Durability of Tenofovir-Based Antiretroviral Therapy in Relation to the Co-Administration of Other Drug Classes in Routine Clinical Practice.
abstract: BACKGROUND
  In clinical trials, toxicity leading to tenofovir disoproxil fumarate (TDF) discontinuation is rare (3% by 2 years); however in clinical practice it seems to be higher, particularly when TDF is co-administered with ritonavir-boosted protease inhibitors (PI/r). Aims of this study were to assess the rate of TDF discontinuations in clinical practice and to identify factors associated with the risk of stopping TDF.
  
  
  METHODS
  All antiretroviral treatment (ART)-naive patients initiating a TDF-based regimen were selected from the ICONA Foundation Study cohort. The primary outcome was TDF discontinuation regardless of the reason; secondary outcome measures were TDF discontinuation due to toxicity and selective TDF discontinuation (that is, TDF discontinuation or substitution, maintaining unchanged the remaining antiretroviral treatment).
  
  
  RESULTS
  3,618 ART-naïve patients were included: 54% started a PI/r-based and 46% a NNRTI-based based regimen. Two-hundred-seventy-seven patients discontinued TDF and reintroduced ART within 30 days without TDF. The probability of TDF discontinuation regardless of the reason was of 7.4% (95%CI:6.4-8.5) by 2 years and 14.1% (95%CI:12.2-16.1) by 5 years. The 5-year KM estimates in the PI/r vs. NNRTI group were 20.4% vs. 7.6%, respectively (log-rank p = 0.0001), for the outcome of stopping regardless of the reason, and 10.7% vs. 4.7% (p = 0.0001) for discontinuation due to toxicity. PI/r use and lower eGFR were associated with an increased risk of discontinuing TDF.
  
  
  CONCLUSIONS
  In our cohort, the frequency of TDF discontinuations was higher than that observed in clinical trials. Co-administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. Further studies are needed to clarify the mechanisms that might have led to this outcome.
authors.affiliation: Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Costarelli
authors.affiliation: Department of Virology, Royal Free and University College Medical School, London, United Kingdom.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.affiliation: Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lapadula
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.affiliation: Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, University of Sassari, Sassari, Italy.
authors.forename: Giordano
authors.initials: G
authors.lastname: Madeddu
authors.affiliation: Department of Infectious Diseases, Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Maggiolo
authors.affiliation: National Institute for Infectious Diseases-IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: Department of Clinical and Biomedical Sciences "Luigi Sacco", Section of Infectious Diseases, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Clinic of Infectious Diseases, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
authors.affiliation: Unit of Infectious Diseases, Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.affiliation: Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage; D000068698:Tenofovir / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D019438:Ritonavir