Drug-discontinuation studies, magnetic resonance imaging studies, and animal studies have produced recent evidence that some antiretroviral therapies may have neurotoxic effects, warranting further research. Individuals who are treated with highly active antiretroviral therapy are at risk for immune reconstitution inflammatory syndrome (IRIS), in which immune recovery triggers clinical deterioration as the newly invigorated immune system reacts to pathogens that either represent ongoing opportunistic infection or were previously successfully controlled. In a population initiating combination antiretroviral therapy between 1999 and 2007, 0.9% developed neurological manifestations of IRIS. Seizures may occur as part of a neurological IRIS syndrome, such as encephalitis and toxoplasmosis.