Intolerance of dolutegravir containing cART regimens in real life clinical practice.

OBJECTIVE: Dolutegravir (DGV) is one of the preferred antiretroviral agents in first line cART. Though considered a well-tolerated drug, we aimed to determine the actual rate, timing, and detailed motivation of stopping DGV in a real life clinical setting.

DESIGN: a cohort study including all patients that started DGV in two HIV treatment centers in the Netherlands.

METHODS: All cART-naïve and cART-experienced patients who had started DGV were identified from the institutional HIV-databases. Clinical data, including motivation and timing of discontinuation of DGV, were extracted from the patient files. Factors that potentially influenced discontinuation of DGV were compared between patients that stopped or continued DGV by multivariate and Kaplan-Meier analyses.

RESULTS: A total of 556 patients were included, of which 102 (18.4%) patients were cART naïve at initiation of DGV. Median follow-up time was 225 days. Overall, in 85 patients (15.3%) DGV was stopped. In 76 patients (13.7%) this was due to intolerability. Insomnia and sleep disturbance (5.6%), gastrointestinal complaints (4.3%) and neuropsychiatric symptoms e.g. anxiety, psychosis and depression (4.3%) were the predominant reasons for switching DGV. In regimens that included abacavir DGV was switched more frequently (adjusted RR 1.92 95%CI 1.09-3.38, p-log-rank 0.01). No virologic failures were observed.

CONCLUSIONS: A relatively high rate of preliminary discontinuation of DGV due to intolerability was detected in our patient population. In particular, DGV was stopped more frequently if the regimen included abacavir. Multiple factors may explain these unexpected post-marketing observations, which warrant further investigation.