Long-term durability of tenofovir-based antiretroviral therapy In relation to the Co-administration of other drug classes in routine clinical practice

Silvia Costarelli, Alessandro Cozzi-Lepri, Giuseppe Lapadula, Stefano Bonora, Giordano Madeddu, Franco Maggiolo, Andrea Antinori, Massimo Galli, Giovanni Di Perri, Pierluigi Viale, Antonella D'Arminio Monforte, Andrea Gori, M. Moroni, M. Andreoni, G. Angarano, F. Castelli, R. Cauda, R. Iardino, G. Ippolito, A. LazzarinC. F. Perno, F. Von Schloesser, A. Castagna, F. Ceccherini-Silberstein, E. Girardi, S. Lo Caputo, C. Mussini, M. Puoti, A. Ammassari, C. Balotta, P. Bonfanti, M. Borderi, M. R. Capobianchi, A. Cingolani, P. Cinque, A. De Luca, A. Di Biagio, N. Gianotti, G. Guaraldi, M. Lichtner, G. Marchetti, S. Marcotullio, L. Monno, E. Quiros Roldan, S. Rusconi, A. Saracino, P. Cicconi, I. Fanti, L. Galli, P. Lorenzini, A. Tavelli, A. Giacometti, A. Costantini, S. Mazzoccato, C. Santoro, C. Suardi, E. Vanino, G. Verucchi, C. Minardi, T. Quirino, C. Abeli, P. E. Manconi, P. Piano, J. Vecchiet, K. Falasca, L. Sighinolfi, D. Segala, F. Mazzotta, G. Cassola, C. Viscoli, A. Alessandrini, R. Piscopo, G. Mazzarello, C. Mastroianni, V. Belvisi, I. Caramma, A. Chiodera, A. P. Castelli, G. Rizzardini, A. L. Ridolfo, R. Piolini, S. Salpietro, L. Carenzi, M. C. Moioli, C. Tincati, C. Puzzolante, N. Abrescia, A. Chirianni, M. G. Guida, M. Gargiulo, F. Baldelli, D. Francisci, G. Parruti, T. Ursini, G. Magnani, M. A. Ursitti, V. Vullo, A. D'Avino, L. Gallo, E. Nicastri, R. Acinapura, M. Capozzi, R. Libertone, G. Tebano, A. Cattelan, L. Sasset, M. S. Mura, B. Rossetti, P. Caramello, G. C. Orofino, M. Sciandra, M. Bassetti, A. Londero, G. Pellizzer, V. Manfrin

Research output: Contribution to journalArticle

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, particularlywhen 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 NNRTIbased 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. Conclusion: 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.

Original languageEnglish
Article numbere0160761
JournalPLoS One
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Costarelli, S., Cozzi-Lepri, A., Lapadula, G., Bonora, S., Madeddu, G., Maggiolo, F., Antinori, A., Galli, M., Di Perri, G., Viale, P., D'Arminio Monforte, A., Gori, A., Moroni, M., Andreoni, M., Angarano, G., Castelli, F., Cauda, R., Iardino, R., Ippolito, G., ... Manfrin, V. (2016). Long-term durability of tenofovir-based antiretroviral therapy In relation to the Co-administration of other drug classes in routine clinical practice. PLoS One, 11(10), [e0160761]. https://doi.org/10.1371/journal.pone.0160761