Lise Cuzin1,2, Pascal Pugliese3, Christine Katlama4,5, Firouzé Bani-Sadr6,7, Tristan Ferry8,9, David Rey10, Jeremy Lourenco11, Sylvie Bregigeon12, Clotilde Allavena13,14, Jacques Reynes15,16, André Cabié1,17. 1. Infectious and Tropical Diseases, Martinique University Hospital, Fort-de-France, France. 2. INSERM UMR1027, Toulouse University, Toulouse, France. 3. Infectious Diseases Department, Nice University Hospital, Nice, France. 4. Sorbonne Univ., UPMC Univ Paris 06-UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris, France. 5. AP-HP, Infectious Diseases Department, APHP Pitié Salpêtrière Hospital, Paris, France. 6. Reims Champagne-Ardenne University, EA-4684/SFR CAPSANTE, Reims, France. 7. Tropical and Infectious Diseases Department, University Hospital Reims, Reims, France. 8. Infectious Disease Unit, Hospices Civils de Lyon, Lyon, France. 9. Claude Bernard Lyon 1 University, CIRI, INSERM U1111, Lyon, France. 10. HIV Infection Care Centre, University Hospital, Strasbourg, France. 11. Infectious Diseases Department, AP-HP-Necker Hospital, Paris, France. 12. Aix Marseille University, APHM Sainte-Marguerite, Marseille, France. 13. Infectious Diseases Department, Nantes University Hospital, Nantes, France. 14. UIC 1413 INSERM, Nantes, France. 15. Infectious Diseases Department, Montpellier University Hospital, Montpellier, France. 16. INSERM U1175, IRD UMI233, Montpellier University, Montpellier, France. 17. INSERM CIC1424, Fort-de-France, France.
Abstract
OBJECTIVES: To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs). METHODS: Patients in 18 HIV reference centres in France were prospectively included in the Dat'AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients' characteristics related to discontinuation due to NPAEs were sought. RESULTS: INSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P < 0.001). Discontinuation for NPAEs occurred in 2.7%, 1.3% and 1.7% of the dolutegravir-, elvitegravir-, and raltegravir-treated patients, respectively (P < 0.001). In the multivariate analysis, discontinuation for NPAEs was related to dolutegravir versus elvitegravir (HR = 2.27; 95% CI 1.63-3.17; P < 0.0001) and versus raltegravir (HR = 2.46; 95% CI 2.00-3.40; P < 0.0001), but neither gender (HR for women = 1.19; 95% CI 0.97-1.46; P = 0.09) nor age (P = 0.12) was related. The association with abacavir was not retained in the final model. CONCLUSIONS: Although discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.
OBJECTIVES: To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs). METHODS:Patients in 18 HIV reference centres in France were prospectively included in the Dat'AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients' characteristics related to discontinuation due to NPAEs were sought. RESULTS: INSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P < 0.001). Discontinuation for NPAEs occurred in 2.7%, 1.3% and 1.7% of the dolutegravir-, elvitegravir-, and raltegravir-treated patients, respectively (P < 0.001). In the multivariate analysis, discontinuation for NPAEs was related to dolutegravir versus elvitegravir (HR = 2.27; 95% CI 1.63-3.17; P < 0.0001) and versus raltegravir (HR = 2.46; 95% CI 2.00-3.40; P < 0.0001), but neither gender (HR for women = 1.19; 95% CI 0.97-1.46; P = 0.09) nor age (P = 0.12) was related. The association with abacavir was not retained in the final model. CONCLUSIONS: Although discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.
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