Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs): data from a real-life setting

Autor: Antonella d'Arminio Monforte, Alessandro, Cozzi-Lepri, DI BIAGIO, Antonio, Giulia, Marchetti, Sergio Lo Caputo, Stefano, Rusconi, Nicola, Gianotti, Valentina, Mazzotta, Giovanni, Mazzarello, Andrea, Costantini, Antonella, Castagna, Andrea, Antinori, A d'Arminio Monforte, Antinori, A, Andreoni, M, Castagna, A, Castelli, F, Cauda, R, G Di Perri, Galli, M, Iardino, R, Ippolito, G, Lazzarin, A, C Marchetti, G, Rezza, G, F von Schloesser, Viale, P, Ceccherini-Silberstein, F, Cozzi-Lepri, A, Girardi, E, S Lo Caputo, Mussini, C, Puoti, M, F Perno, C, Balotta, C, Bandera, A, Bonora, S, Borderi, M, Calcagno, A, Capetti, A, R Capobianchi, M, Cicalini, S, Cingolani, A, Cinque, P, A De Luca, A Di Biagio, Gianotti, N, Gori, A, Guaraldi, G, Lapadula, G, Lichtner, M, Madeddu, G, Maggiolo, F, Marchetti, G, Monno, L, Nozza, S, Pinnetti, C, E Quiros Roldan, Rossotti, R, Rusconi, S, M Santoro, M, Saracino, A, Sarmati, L, Fanti, I, Galli, L, Lorenzini, P, Rodan(`(o))', A, Macchia, M, Tavelli, A, Carletti, F, Carrara, S, A Di Caro, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Fabrizio, C, Suardi, C, Donati, V, Verucchi, G, Castelnuovo, F, Minardi, C, Menzaghi, B, Abeli, C, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Blanc, P, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Pozzetto, I, Bonfanti, P, Molteni, C, Chiodera, A, Milini, P, Nunnari, G, Pellican(`(o)), G, Rizzardini, G, Bai, F, C Moioli, M, Piolini, R, L Ridolfo, A, Salpietro, S, Tincati, C, Puzzolante, C, Migliorino, C, Sangiovanni, V, Borgia, G, Esposito, V, F Di Martino, Gentile, I, Maddaloni, L, M Cattelan, A, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, A Ursitti, M, Cristaudo, A, Vullo, V, Acinapura, R, Baldin, G, Capozzi, M, Mondi, A, M Rivano Capparucia, Iaiani, G, Latini, A, Gagliardini, R, M Plazzi, M, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, R Fontana Del Vecchio, Francisci, D, C Di Giuli, Caramello, P, C Orofino, G, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, A Ialungo and
Přispěvatelé: d'Arminio Monforte, Antonella, Cozzi-Lepri, Alessandro, Di Biagio, Antonio, Marchetti, Giulia, Lo Caputo, Sergio, Rusconi, Stefano, Gianotti, Nicola, Mazzotta, Valentina, Mazzarello, Giovanni, Costantini, Andrea, Castagna, Antonella, Antinori, Andrea
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Integrase inhibitor
hiv
HIV Infections
Quinolones
Piperazines
Settore MED/07
Cohort Studies
chemistry.chemical_compound
0302 clinical medicine
HIV Seropositivity
Pharmacology (medical)
030212 general & internal medicine
Treatment Failure
risk reduction
cd4 count
toxic effect
Elvitegravir
cox proportional hazards models
Cobicistat
hiv
cd4 count
determination procedure
hiv seropositivity
integrase inhibitors
plasma
treatment failure
virology
toxic effect
risk reduction
cox proportional hazards models
elvitegravir
raltegravir
surrogate endpoints
cobicistat
dolutegravir
time-to-treatment

Middle Aged
virology
dolutegravir
Infectious Diseases
integrase inhibitors
Italy
Dolutegravir
hiv
cd4 count determination procedure
hiv seropositivity
integrase inhibitors
plasma
treatment failure
virology
toxic effect
risk reduction
cox proportional hazards models
elvitegravir
raltegravir
surrogate endpoints
cobicistat
dolutegravir
time-to-treatment

elvitegravir
Regression Analysis
Female
raltegravir
Heterocyclic Compounds
3-Ring

medicine.drug
Microbiology (medical)
Adult
medicine.medical_specialty
Pyridones
030106 microbiology
time-to-treatment
Lower risk
03 medical and health sciences
Internal medicine
Raltegravir Potassium
Oxazines
medicine
Humans
HIV Integrase Inhibitors
plasma
Pharmacology
business.industry
Surrogate endpoint
Raltegravir
Survival Analysis
Discontinuation
CD4 Lymphocyte Count
chemistry
determination procedure
surrogate endpoints
business
Zdroj: The Journal of antimicrobial chemotherapy. 74(5)
ISSN: 1460-2091
Popis: Objectives To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ART-naive individuals. Methods The study design was observational. Patients were HIV-positive, ART-naive subjects starting raltegravir, elvitegravir/cobicistat or dolutegravir with two NRTIs. The primary endpoint was time to treatment failure, i.e. occurrence of virological failure (first of two consecutive plasma HIV RNAs ≥200 copies/mL after 24 weeks) or INSTI discontinuation for any reason apart from simplification. Secondary endpoints were INSTI discontinuation due to toxicity/intolerance and CD4 count response. Survival analysis was done using Kaplan-Meier and Cox regression. Results Two thousand and sixteen patients were included: 310 (15.4%) started raltegravir-based regimens, 994 (49.3%) started dolutegravir-based regimens and 712 (35.3%) started elvitegravir/cobicistat-based regimens. Over a median of 11 months, 167 patients experienced treatment failure; the 1 year probability of treatment failure was 6.5% for raltegravir, 5.4% for dolutegravir and 6.7% for elvitegravir/cobicistat (P = 0.001). Sixty-eight patients (3.4%) discontinued INSTIs owing to toxicity/intolerance. By multivariable analysis, patients starting raltegravir had a 2.03-fold (95% CI = 1.2-3.2) higher risk and patients on elvitegravir/cobicistat a 1.88-fold (95% CI = 1.2-2.9) higher risk of treatment failure versus dolutegravir; there was no difference in risk of discontinuation due to toxicity/intolerance when comparing dolutegravir and raltegravir and marginal evidence for a difference when comparing elvitegravir/cobicistat and dolutegravir (adjusted relative hazard = 1.94 for elvitegravir/cobicistat versus dolutegravir, 95% CI = 1.00-3.76, P = 0.05). Conclusions In our real-life setting, INSTI-based regimens showed high potency and durability. Among regimens currently recommended in Europe, those including dolutegravir are associated with a lower risk of treatment failure.
Databáze: OpenAIRE