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Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe
Authors:JR Santos  A Cozzi‐Lepri  A Phillips  S De Wit  C Pedersen  P Reiss  A Blaxhult  A Lazzarin  M Sluzhynska  C Orkin  C Duvivier  J Bogner  P Gargalianos‐Kakolyris  P Schmid  G Hassoun  I Khromova  M Beniowski  V Hadziosmanovic  D Sedlacek  R Paredes  JD Lundgren
Affiliation:1. Fight Against AIDS Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain;2. Royal Free and University College, London, UK;3. Centre Hospitalier Universitaire Saint‐Pierre, Brussels, Belgium;4. Odense University Hospital, Odense, Denmark;5. Academic Medical Center, Amsterdam, the Netherlands;6. Karolinska Institute, Venh?lsan, Stockholm, Sweden;7. San Raffaele Scientific Institute, Milan, Italy;8. Lviv Regional HIV/AIDS Prevention and Control Centre, Kiev, Ukraine;9. Royal London Hospital, London, UK;10. H?pital Necker‐Enfants Malades, Paris, France;11. Medizinische Poliklinik, Munchen, Germany;12. The General Hospital of Athens “G. Gennimatas”, Athens, Greece;13. Cantonal Hospital St. Gallen, St. Gallen, Switzerland;14. Rambam Health Care Campus, Haifa, Israel;15. Centre for HIV/AIDS and Infectious Diseases, Moscow, Russia;16. Szpital Specjalistyczny, Chorzow, Poland;17. Klinicki Centar Univerziteta Sarajevo (KCUS), Sarajevo, Bosnia & Herzegovina;18. Charles University Hospital, Plzen, Czech Republic;19. IrsiCaixa AIDS Research Institute, Barcelona, Spain;20. Universitat de Vic‐Universitat Central de Catalunya, Barcelona, Spain;21. Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
Abstract:

Objectives

The aim of the study was to evaluate the long‐term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)‐, darunavir/ritonavir (DRV/r)‐, and lopinavir/ritonavir (LPV/r)‐containing regimens.

Methods

Data were analysed for 5678 EuroSIDA‐enrolled patients starting a DRV/r‐, ATZ/r‐ or LPV/r‐containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART‐naïve subjects (8%) at ritonavir‐boosted protease inhibitor (PI/r) initiation; (2) ART‐experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV‐1 RNA copies/mL; and (3) ART‐experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan–Meier and multivariable Cox models were used to compare risks of failure by PI/r‐based regimen. The main analysis was performed with intention‐to‐treat (ITT) ignoring treatment switches.

Results

The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log‐rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART‐naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment‐experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r‐based ART.

Conclusions

Although confounding by indication and calendar year cannot be completely ruled out, in ART‐experienced subjects the long‐term effectiveness of DRV/r‐containing regimens appears to be greater than that of ATZ/r and LPV/r.
Keywords:antiretroviral therapy‐experienced patients  antiretroviral therapy‐naï  ve patients  atazanavir/ritonavir  darunavir/ritonavir  lopinavir/ritonavir
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