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.
Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe / Santos, J. R.; Cozzi-Lepri, A.; Phillips, A.; De Wit, S.; Pedersen, C.; Reiss, P.; Blaxhult, A.; Lazzarin, A.; Sluzhynska, M.; Orkin, C.; Duvivier, C.; Bogner, J.; Gargalianos-Kakolyris, P.; Schmid, P.; Hassoun, G.; Khromova, I.; Beniowski, M.; Hadziosmanovic, V.; Sedlacek, D.; Paredes, R.; Lundgren, J. D.; Losso, M.; Kundro, M.; Schmied, B.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Begovac, J.; Machala, L.; Jilich, D.; Kronborg, G.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Moller, N. F.; Ostergaard, L.; Wiese, L.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Ristola, M.; Aho, I.; Viard, J. -P.; Girard, P. -M.; Pradier, C.; Fontas, E.; Rockstroh, J.; Schmidt, R.; Degen, O.; Stellbrink, H. J.; Stefan, C.; Fatkenheuer, G.; Chkhartishvili, N.; Gargalianos, P.; Xylomenos, G.; Lourida, P.; Sambatakou, H.; Szlavik, J.; Gottfredsson, M.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Shahar, E.; Elinav, H.; Haouzi, M.; Elbirt, D.; Sthoeger, Z. M.; D'Arminio Monforte, A.; Esposito, R.; Mazeu, I.; Mussini, C.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Zaccarelli, M.; Antinori, A.; Acinapura, R.; Plazzi, M.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Uzdaviniene, V.; Matulionyte, R.; Staub, T.; Hemmer, R.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Horban, A.; Bakowska, E.; Flisiak, R.; Grzeszczuk, A.; Parczewski, M.; Pynka, M.; Maciejewska, K.; Mularska, E.; Smiatacz, T.; Gensing, M.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Mozer-Lisewska, I.; Caldeira, L.; Mansinho, K.; Maltez, F.; Radoi, R.; Panteleev, A.; Panteleev, O.; Yakovlev, A.; Trofimora, T.; Kuzovatova, E.; Borodulina, E.; Vdoushkina, E.; Jevtovic, D.; Tomazic, J.; Gatell, J. M.; Miro, J. M.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Tural, C.; Puig, J.; Bravo, I.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Falconer, K.; Thalme, A.; Sonnerborg, A.; Flamholc, L.; Scherrer, A.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Kuznetsova, A.; Kyselyova, G.; Gazzard, B.; Johnson, A. M.; Simons, E.; Edwards, S.; Johnson, M. A.; Mocroft, A.; Weber, J.; Scullard, G.; Clarke, A.; Leen, C.; Gatell, J.; Ledergerber, B.; Kirk, O.; Peters, L.; Matthews, C.; Fischer, A. H.; Bojesen, A.; Raben, D.; Kristensen, D.; Gronborg Laut, K.; Larsen, J. F.; Podlekareva, D.; Shepherd, L.; Schultze, A.; Thiebaut, R.; Burger, D.. - In: HIV MEDICINE. - ISSN 1464-2662. - 19:5(2018), pp. 324-338. [10.1111/hiv.12581]
Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe
Schmidt R.;Burke M.;Mussini C.Membro del Collaboration Group
;Zaccarelli M.;
2018
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.Pubblicazioni consigliate
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