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 / J.R. 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, J.D. Lundgren, M. Losso, M. Kundro, B. Schmied, R. Zangerle, I. Karpov, A. Vassilenko, V.M. Mitsura, D. Paduto, N. Clumeck, M. Delforge, E. Florence, L. Vandekerckhove, J. Begovac, L. Machala, D. Jilich, G. Kronborg, T. Benfield, J. Gerstoft, T. Katzenstein, N.F. Moller, L. Ostergaard, L. Wiese, L.N. Nielsen, K. Zilmer, J. Smidt, M. Ristola, I. Aho, J.-. Viard, P.-. Girard, C. Pradier, E. Fontas, J. Rockstroh, R. Schmidt, O. Degen, H.J. Stellbrink, C. Stefan, G. Fatkenheuer, N. Chkhartishvili, P. Gargalianos, G. Xylomenos, P. Lourida, H. Sambatakou, J. Szlavik, M. Gottfredsson, F. Mulcahy, I. Yust, D. Turner, M. Burke, E. Shahar, H. Elinav, M. Haouzi, D. Elbirt, Z.M. Sthoeger, A. D'Arminio Monforte, R. Esposito, I. Mazeu, C. Mussini, F. Mazzotta, A. Gabbuti, V. Vullo, M. Lichtner, M. Zaccarelli, A. Antinori, R. Acinapura, M. Plazzi, A. Castagna, N. Gianotti, M. Galli, A. Ridolfo, B. Rozentale, V. Uzdaviniene, R. Matulionyte, T. Staub, R. Hemmer, V. Ormaasen, A. Maeland, J. Bruun, B. Knysz, J. Gasiorowski, M. Inglot, A. Horban, E. Bakowska, R. Flisiak, A. Grzeszczuk, M. Parczewski, M. Pynka, K. Maciejewska, E. Mularska, T. Smiatacz, M. Gensing, E. Jablonowska, E. Malolepsza, K. Wojcik, I. Mozer-Lisewska, L. Caldeira, K. Mansinho, F. Maltez, R. Radoi, A. Panteleev, O. Panteleev, A. Yakovlev, T. Trofimora, E. Kuzovatova, E. Borodulina, E. Vdoushkina, D. Jevtovic, J. Tomazic, J.M. Gatell, J.M. Miro, S. Moreno, J.M. Rodriguez, B. Clotet, A. Jou, C. Tural, J. Puig, I. Bravo, P. Domingo, M. Gutierrez, G. Mateo, M.A. Sambeat, J.M. Laporte, K. Falconer, A. Thalme, A. Sonnerborg, L. Flamholc, A. Scherrer, R. Weber, M. Cavassini, A. Calmy, H. Furrer, M. Battegay, A. Kuznetsova, G. Kyselyova, B. Gazzard, A.M. Johnson, E. Simons, S. Edwards, M.A. Johnson, A. Mocroft, J. Weber, G. Scullard, A. Clarke, C. Leen, J. Gatell, B. Ledergerber, O. Kirk, L. Peters, C. Matthews, A.H. Fischer, A. Bojesen, D. Raben, D. Kristensen, K. Gronborg Laut, J.F. Larsen, D. Podlekareva, L. Shepherd, A. Schultze, R. Thiebaut, D. Burger. - 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
A. D'Arminio Monforte;M. Galli;
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.File | Dimensione | Formato | |
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