Background: In 2016 an unexpectedly high frequency of dolutegravir (DTG) discontinuation for neuropsychiatric reasons was reported, these effects might be more frequent when DTG was used with abacavir (ABC), in women, or in ageing people. Our objective was to search in our large prospectively collected cohort the patients who were treated with an integrase inhibitor (INSTI) and to analyze the frequency and causes of discontinuation.
Methods: The Dat''AIDS cohort is prospectively collected in 18 HIV reference centers in France. Data for all patients starting an INSTI containing regimen between 01/01/2006 and 31/12/2016 were extracted. All causes - chosen by the physician in a limited list of items - of an INSTI containing regimen discontinuation were analyzed, and patients'' characteristics related with discontinuation due to neuropsychiatric side effects were searched for.
Results: INSTI were prescribed to 21 315 patients: 6 274 treated with DLT, 3 421 with elvitegravir boosted by cobicistat (EVG/c), and 11 620 with raltegravir (RAL), see Table 1. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the DTG, EVG/c, and RAL treated patients, respectively (p< 0.001). The main reason for DTG and EVG/c discontinuation was intolerance (respectively 7.1% and 9.4% of the patients, p< 0.001). For RAL, treatment simplification (18.7%) was the leading reason. Discontinuation for neuropsychiatric reasons was described in respectively 2.7%, 1.3% and 1.7% of the DTG, EVG/c and RAL treated patients (p< 0.001). In multivariate analysis, discontinuation for a neuropsychiatric reason was related to DTG - versus EVG/C (HR=2.27; 95%CI 1.63-3.17; p< 0.0001) and versus RAL (HR=2.46; 95%CI 2.00-3.40; p< 0.0001), while neither gender (HR for women=1.19; 95%CI 0.97-1.46; p=0.09) nor age (p=0.12) were related. The association with abacavir was not retained in the final model, due to a confusion factor, most of the patients treated by DTG receiving ABC whereas none of the patients treated by EVG/c and few of those treated by RAL did.
Conclusions: Although discontinuation for side effects was less frequent with DTG than with EVG/c, neuropsychiatric side effects were more frequent with DTG, but still remained rare (2.7%). No patient''s characteristic could be related with these side effects in this very large population.

  DLT N = 6 274EVG/c N = 3 421RAL N = 11 620
Gender (% women) 28.526.729.7
Age (years)<4025.640.823.1
Associated NRTIABC66.4017.6
Lenght of known infectionmedian (25-75IQ)12 (4-20)7 (1-16)14 (7-20)
[Patients characteristics at the time of INSTI initiation]

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