PMID- 30688007 OWN - NLM STAT- MEDLINE DCOM- 20200427 LR - 20210826 IS - 1468-1293 (Electronic) IS - 1464-2662 (Linking) VI - 20 IP - 3 DP - 2019 Mar TI - Discontinuation of dolutegravir, elvitegravir/cobicistat and raltegravir because of toxicity in a prospective cohort. PG - 237-247 LID - 10.1111/hiv.12710 [doi] AB - 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. CI - (c) 2019 British HIV Association. FAU - Llibre, J M AU - Llibre JM AUID- ORCID: 0000-0002-7158-6753 AD - Infectious Diseases and "Fight AIDS" Foundation, University Hospital Germans Trias i Pujol, Badalona, Spain. FAU - Montoliu, A AU - Montoliu A AD - Statistics and Epidemiology, Centre d'Estudis Epidemiologics sobre les ITS i la Sida de Catalunya (CEEISCAT, CIBERESP), Badalona, Spain. FAU - Miro, J M AU - Miro JM AD - Hospital Clinic- IDIBAPS, University of Barcelona, Barcelona, Spain. FAU - Domingo, P AU - Domingo P AD - Infectious Diseases, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. FAU - Riera, M AU - Riera M AD - Hospital Son Espases, Palma de Mallorca, Spain. FAU - Tiraboschi, J AU - Tiraboschi J AUID- ORCID: 0000-0002-0073-873X AD - Infectious Diseases, Hospital Universitari de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. FAU - Curran, A AU - Curran A AD - Infectious Diseases, Hospital Universitari Vall d'Hebron, Barcelona, Spain. FAU - Homar, F AU - Homar F AD - Hospital Son Llatzer, Palma de Mallorca, Spain. FAU - Ambrosioni, J AU - Ambrosioni J AD - Hospital Clinic- IDIBAPS, University of Barcelona, Barcelona, Spain. FAU - Abdulghani, N AU - Abdulghani N AD - Hospital de Santa Maria, Lleida, Spain. FAU - Force, L AU - Force L AD - Internal Medicine, Hospital de Mataro-Consorci Sanitari del Maresme, Mataro, Spain. FAU - Peraire, J AU - Peraire J AD - Internal Medicine, Hospital Joan XXIII, Tarragona, Spain. FAU - Casabona, J AU - Casabona J AD - Statistics and Epidemiology, Centre d'Estudis Epidemiologics sobre les ITS i la Sida de Catalunya (CEEISCAT, CIBERESP), Badalona, Spain. CN - PISCIS Cohort group LA - eng GR - IDIBAPS/International GR - ViiV Healthcare/International PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20190127 PL - England TA - HIV Med JT - HIV medicine JID - 100897392 RN - 0 (Heterocyclic Compounds, 3-Ring) RN - 0 (Oxazines) RN - 0 (Piperazines) RN - 0 (Pyridones) RN - 0 (Quinolones) RN - 43Y000U234 (Raltegravir Potassium) RN - 4GDQ854U53 (elvitegravir) RN - DKO1W9H7M1 (dolutegravir) RN - LW2E03M5PG (Cobicistat) SB - IM MH - Adult MH - CD4 Lymphocyte Count MH - Cobicistat/administration & dosage/*adverse effects MH - Female MH - HIV Infections/*drug therapy/immunology MH - Heterocyclic Compounds, 3-Ring/administration & dosage/*adverse effects MH - Humans MH - Male MH - Middle Aged MH - Oxazines MH - Piperazines MH - Proportional Hazards Models MH - Prospective Studies MH - Pyridones MH - Quinolones/administration & dosage/*adverse effects MH - Raltegravir Potassium/administration & dosage/*adverse effects MH - Spain OTO - NOTNLM OT - adverse events OT - dolutegravir OT - elvitegravir/cobicistat OT - integrase strand transfer inhibitors OT - neuropsychiatric toxicity OT - raltegravir FIR - Vilaro, Joaquim IR - Vilaro J FIR - Masabeu, Angels IR - Masabeu A FIR - Orti, Amat J IR - Orti AJ FIR - Dalmau, David IR - Dalmau D FIR - Reyes, Juliana IR - Reyes J FIR - Bruguera, Andreu IR - Bruguera A FIR - Montoliu, Alexandra IR - Montoliu A FIR - Muntada, Esteve IR - Muntada E FIR - Podzamczer, D IR - Podzamczer D FIR - Navarro, G IR - Navarro G FIR - Cortes, C IR - Cortes C FIR - Falco, V IR - Falco V FIR - Mallolas, J IR - Mallolas J FIR - Manzardo, C IR - Manzardo C FIR - Imaz, A IR - Imaz A FIR - Burgos, J IR - Burgos J FIR - Gracia Mateo, M IR - Gracia Mateo M FIR - Gutierrez, M M IR - Gutierrez MM FIR - Murillas, J IR - Murillas J FIR - Segura, F IR - Segura F FIR - Garcia-Gasalla, M IR - Garcia-Gasalla M FIR - Puig, T IR - Puig T FIR - Vidal, F IR - Vidal F FIR - Leon, E IR - Leon E FIR - Jaen, A IR - Jaen A FIR - Almuedo, A IR - Almuedo A FIR - De Lazzari, E IR - De Lazzari E FIR - Giralt, D IR - Giralt D FIR - Martin, M IR - Martin M FIR - Gargoulas, F IR - Gargoulas F FIR - Vanrell, T IR - Vanrell T FIR - Rubia, J C IR - Rubia JC FIR - Vila, J IR - Vila J FIR - Ferres, M IR - Ferres M FIR - Morell, B IR - Morell B FIR - Tamayo, M IR - Tamayo M FIR - Laguno, M IR - Laguno M FIR - Martinez, M IR - Martinez M FIR - Blanco, J L IR - Blanco JL FIR - Garcia-Alcaide, F IR - Garcia-Alcaide F FIR - Martinez, E IR - Martinez E FIR - Jou, A IR - Jou A FIR - Clotet, B IR - Clotet B FIR - Saumoy, M IR - Saumoy M FIR - Silva, A IR - Silva A FIR - Prieto, P IR - Prieto P FIR - Navarro, J IR - Navarro J FIR - Ribera, Esteve IR - Ribera E FIR - Gurgui, M IR - Gurgui M FIR - Ribas, M A IR - Ribas MA FIR - Campins, A A IR - Campins AA FIR - Fanjul, F J IR - Fanjul FJ FIR - Leyes, M IR - Leyes M FIR - Penaranda, M IR - Penaranda M FIR - Martin, L IR - Martin L FIR - Vilchez, H IR - Vilchez H FIR - Calzado, S IR - Calzado S FIR - Cervantes, M IR - Cervantes M FIR - Amengual, J IR - Amengual J FIR - Navarro, M IR - Navarro M FIR - Payeras, T IR - Payeras T FIR - Cifuentes, C IR - Cifuentes C FIR - Comella, T IR - Comella T FIR - Vargas, M IR - Vargas M FIR - Vilades, C IR - Vilades C FIR - Barrufet, P IR - Barrufet P FIR - Chivite, I IR - Chivite I FIR - Chamarro, E IR - Chamarro E FIR - Escrig, C IR - Escrig C FIR - Cairo, M IR - Cairo M FIR - Martinez-Lacasa, X IR - Martinez-Lacasa X FIR - Font, R IR - Font R FIR - Deig, E IR - Deig E FIR - Meyer, S IR - Meyer S FIR - Hernandez, J IR - Hernandez J EDAT- 2019/01/29 06:00 MHDA- 2020/04/28 06:00 CRDT- 2019/01/29 06:00 PHST- 2018/12/04 00:00 [accepted] PHST- 2019/01/29 06:00 [pubmed] PHST- 2020/04/28 06:00 [medline] PHST- 2019/01/29 06:00 [entrez] AID - 10.1111/hiv.12710 [doi] PST - ppublish SO - HIV Med. 2019 Mar;20(3):237-247. doi: 10.1111/hiv.12710. Epub 2019 Jan 27.