Dolutegravir Neuropsychiatric Adverse Events: Specific Drug Effect or Class Effect

Integrase strand transfer inhibitors (INSTIs) are a newer class of antiretroviral treatment for HIV-infected patient. INSTIs currently available for use are raltegravir, elvitegravir, dolutegravir (DTG), and bictegravir. Clinical studies using INSTIs have demonstrated an 80-90% efficiency in treating HIV-positive antiretroviral therapy - naive patients. They are recommended by internatioal guidelines as the preferred agents for the first-line regimen. INSTIs have also been demonstrated as safe and tolerable. In clinical trials, the rate of adverse events (AEs) such as neuropsychiatric AEs (NPSAEs) leading to discontinuation is very low. However, recent published cohort studies show growing concerns on DTG induced NPSAEs. In this paper, we will review available evidence about DTG - NPSAEs and analyze whether the backbone (abacavir or tenofovir) matters as well as discussing the possible mechanism behind this toxicity.