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Neuropsychiatric Adverse Events with Dolutegravir and Other Integrase Strand Transfer Inhibitors
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Christian Hoffmann, ICH Study Center Hamburg, Germany; Department of Medicine II, University of Schleswig-Holstein, Campus Kiel, Germany
Josep M. Llibre,
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Abstract
Neuropsychiatric adverse events (NPAEs) observed with the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) are usually mild to moderate. The most prevalent symptoms are insomnia and sleep disorders, but the spectrum also includes dizziness, anxiety, depression, headache, paraesthesia, muscleskeletal pain, poor concentration, and slow thinking. In recent cohort studies involving >6400 patients in different countries, discontinuation rates due to NPAEs were observed in around 3.5% (range, 1.4-7.2%) of subjects treated with DTG. These rates have been higher than those seen in randomized clinical trials and were also higher than with other INSTIs such as elvitegravir or raltegravir. Elderly, female patients and those who initiate abacavir simultaneously appear to be more vulnerable in some cohorts. It remains unclear if NPAEs are driven by an increased DTG exposure. With heightened awareness of health-care providers and patients, reports of NPAEs will probably increase in the future.
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