Objectives: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ARTnaive 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.

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

Cacopardo B;
2019-01-01

Abstract

Objectives: To evaluate the durability of three integrase strand transfer inhibitors (INSTIs) and two NRTIs in ARTnaive 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.
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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/361181
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