Discontinuation of dolutegravir, elvitegravir/cobicistat and raltegravir because of toxicity in a prospective cohort
Por:
Montoliu, A, Miro, JM, Domingo, P, Riera, M, Curran, A, Homar, F, Ambrosioni, J, Abdulghani, N, Force, L, Peraire, J, Vilaro, J, Masabeu, A, Orti, AJ, Dalmau, D, Casabona, J, Reyes, J, Bruguera, A, Muntada, E, Podzamczer, D, Llibre, JM, Navarro, G, Cortes, C, Falco, V, Mallolas, J, Manzardo, C, Imaz, A, Tiraboschi, J, Burgos, J, Mateo, MG, Gutierrez, MM, Murillas, J, Segura, F, Garcia-Gasalla, M, Puig, T, Vidal, F, Leon, E, Jaen, A, Almuedo, A, De Lazzari, E, Giralt, D, Martin, M, Gargoulas, F, Vanrell, T, Rubia, JC, Vila, J, Ferres, M, Morell, B, Tamayo, M, Laguno, M, Martinez, M, Blanco, JL, Garcia-Alcaide, F, Rojas, J, Martinez, E, Jou, A, Clotet, B, Saumoy, M, Silva, A, Prieto, P, Ribera, JNIE, Gurgui, M, Campins, AA, Fanjul, FJ, Leyes, M, Penaranda, M, Martin, L, Vilchez, H, Calzado, S, Cervantes, M, Amengual, MJ, Navarro, M, Payeras, T, Cifuentes, C, Comella, T, Vargas, M, Vilades, C, Barrufet, P, Chivite, I, Chamarro, E, Escrig, C, Cairo, M, Martinez-Lacasa, X, Font, R, Deig, E, Meyer, S, Hernandez, J
Publicada:
1 mar 2019
Resumen:
Objectives The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. Methods A population-based, prospective, multicentre cohort study was carried out. Treatment-naive subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA < 50 HIV-1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double-checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. Results A total of 4165 subjects (37% treatment-naive) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. Conclusions In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.
Filiaciones:
Montoliu, A:
CEEISCAT, CIBERESP, Stat & Epidemiol, Badalona, Spain
CEEISCAT, Badalona, Spain
Miro, JM:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Domingo, P:
Hosp Santa Creu & Sant Pau, Infect Dis, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Riera, M:
Hosp Son Espases, Palma De Mallorca, Spain
Hosp Son Espases Mallorca, Palma De Mallorca, Spain
Curran, A:
Hosp Univ Vall dHebron, Infect Dis, Barcelona, Spain
Hosp Univ Vall dHebron, Barcelona, Spain
Homar, F:
Hosp Son Llatzer, Palma De Mallorca, Spain
Ambrosioni, J:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Abdulghani, N:
Hosp Santa Maria, Lleida, Spain
Force, L:
Hosp Mataro Consorci Sanitari Maresme, Internal Med, Mataro, Spain
Hosp Mataro Consorci Sanitari Maresme, Mataro, Spain
Peraire, J:
Hosp Joan 23, Internal Med, Tarragona, Spain
Hosp Joan 23, Tarragona, Spain
Vilaro, J:
Hosp Gen Vic, Vic, Spain
Masabeu, A:
Hosp Palamos, Palamos, Spain
Orti, AJ:
Hosp Verge Cinta, Tortosa, Spain
Hosp Verge Cinta Tortosa, Tortosa, Spain
Dalmau, D:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Casabona, J:
CEEISCAT, CIBERESP, Stat & Epidemiol, Badalona, Spain
CEEISCAT, CIBERESP, Badalona, Spain
Reyes, J:
CEEISCAT, Badalona, Spain
Bruguera, A:
CEEISCAT, Badalona, Spain
Muntada, E:
CEEISCAT, Badalona, Spain
Podzamczer, D:
Hosp Univ Bellvitge, IDIBELL, Barcelona, Spain
Llibre, JM:
Univ Hosp Germans Trias & Pujol, Infect Dis & Fight AIDS Fdn, Badalona, Spain
Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Fdn Lluita Sida, Barcelona, Spain
Navarro, G:
Univ Autonoma Barcelona, Corp Sanitaria & Univ Parc Tauli, Barcelona, Spain
Cortes, C:
Consorci Sanitari Integral, Barcelona, Spain
Falco, V:
Hosp Univ Vall dHebron, Barcelona, Spain
Mallolas, J:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Manzardo, C:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Imaz, A:
Hosp Univ Bellvitge, IDIBELL, Barcelona, Spain
Tiraboschi, J:
Hosp Univ Bellvitge, IDIBELL, Infect Dis, Barcelona, Spain
Hosp Univ Bellvitge, IDIBELL, Barcelona, Spain
Burgos, J:
Hosp Univ Vall dHebron, Barcelona, Spain
Mateo, MG:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Gutierrez, MM:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Murillas, J:
Hosp Son Espases Mallorca, Palma De Mallorca, Spain
Segura, F:
Univ Autonoma Barcelona, Corp Sanitaria & Univ Parc Tauli, Barcelona, Spain
Garcia-Gasalla, M:
Hosp Son Llatzer, Palma De Mallorca, Spain
Puig, T:
Hosp Santa Maria, Lleida, Spain
Vidal, F:
Hosp Joan 23, Tarragona, Spain
Leon, E:
Consorci Sanitari Integral, Barcelona, Spain
Jaen, A:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Almuedo, A:
Hosp Gen Granollers, Granollers, Spain
De Lazzari, E:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Giralt, D:
Hosp Univ Bellvitge, IDIBELL, Barcelona, Spain
Martin, M:
Hosp Univ Vall dHebron, Barcelona, Spain
Gargoulas, F:
Hosp Son Espases, Palma De Mallorca, Spain
Hosp Son Llatzer, Palma De Mallorca, Spain
Vanrell, T:
Hosp Son Espases, Palma De Mallorca, Spain
Hosp Son Llatzer, Palma De Mallorca, Spain
Rubia, JC:
Consorci Sanitari Integral, Barcelona, Spain
Vila, J:
Serv Salut Integrats Baix Emporda, Palamos, Spain
Ferres, M:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Morell, B:
Hosp Santa Maria, Lleida, Spain
Tamayo, M:
Hosp Gen Granollers, Granollers, Spain
Laguno, M:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Martinez, M:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Blanco, JL:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Garcia-Alcaide, F:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Rojas, J:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Martinez, E:
Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain
Jou, A:
Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Fdn Irsicaixa, Fdn Lluita Sida, Barcelona, Spain
Clotet, B:
Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Fdn Irsicaixa, Fdn Lluita Sida, Barcelona, Spain
Saumoy, M:
Hosp Univ Bellvitge, IDIBELL, Barcelona, Spain
Silva, A:
Hosp Univ Bellvitge, IDIBELL, Barcelona, Spain
Prieto, P:
Hosp Univ Bellvitge, IDIBELL, Barcelona, Spain
Ribera, JNIE:
Hosp Univ Vall dHebron, Barcelona, Spain
Gurgui, M:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Campins, AA:
Hosp Son Espases Mallorca, Palma De Mallorca, Spain
Fanjul, FJ:
Hosp Son Espases Mallorca, Palma De Mallorca, Spain
Leyes, M:
Hosp Son Espases Mallorca, Palma De Mallorca, Spain
Penaranda, M:
Hosp Son Espases Mallorca, Palma De Mallorca, Spain
Martin, L:
Hosp Son Espases Mallorca, Palma De Mallorca, Spain
Vilchez, H:
Hosp Son Espases Mallorca, Palma De Mallorca, Spain
Calzado, S:
Univ Autonoma Barcelona, Corp Sanitaria & Univ Parc Tauli, Barcelona, Spain
Cervantes, M:
Univ Autonoma Barcelona, Corp Sanitaria & Univ Parc Tauli, Barcelona, Spain
Amengual, MJ:
Univ Autonoma Barcelona, Corp Sanitaria & Univ Parc Tauli, Barcelona, Spain
Navarro, M:
Univ Autonoma Barcelona, Corp Sanitaria & Univ Parc Tauli, Barcelona, Spain
Payeras, T:
Hosp Son Llatzer, Palma De Mallorca, Spain
Cifuentes, C:
Hosp Son Llatzer, Palma De Mallorca, Spain
Comella, T:
Hosp Santa Maria, Lleida, Spain
Vargas, M:
Hosp Joan 23, Tarragona, Spain
Vilades, C:
Hosp Joan 23, Tarragona, Spain
Barrufet, P:
Hosp Mataro Consorci Sanitari Maresme, Mataro, Spain
Chivite, I:
Consorci Sanitari Integral, Barcelona, Spain
Chamarro, E:
Hosp Verge Cinta Tortosa, Tortosa, Spain
Escrig, C:
Hosp Verge Cinta Tortosa, Tortosa, Spain
Cairo, M:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Martinez-Lacasa, X:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Font, R:
Hosp Univ Mutua Terrassa, Terrassa, Spain
Deig, E:
Hosp Gen Granollers, Granollers, Spain
Meyer, S:
Comite 1er Desembre, Barcelona, Spain
Hernandez, J:
Comite 1er Desembre, Barcelona, Spain
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