ART Intensification Is not Effective as a Treatment for Neurocognitive Impairment in People Living with HIV on Suppressive ART

Many people with HIV suffer with neurocognitive impairment even though they take antiretroviral therapy (ART). This might be due to replication of HIV in the central nervous system even when the virus is undetectable in blood. In addition, some ART medications like dolutegravir could negatively impact cognition or mood.

As part of A5324, 191 people living with HIV with neurocognitive impairment and with an undetectable viral load were enrolled in a randomized, double-blind, placebo-controlled trial of ART intensification. Participants received drugs (dolutegravir+/-maraviroc) or placebo in addition to their standard ART regimen and were followed for two years to determine if their neurocognitive performance, mood, daily functioning, or weight would change over time.

Study drugs were generally safe and were stopped due to an adverse event in 15 participants but did not differ between arms. Neurocognitive performance, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later.

The findings do not support ART intensification as a treatment for neurocognitive impairment in people living with HIV on suppressive ART and speak against ongoing viral replication in the central nervous system. They also do not support the idea that dolutegravir adversely affects cognition, mood, or weight. It is reassuring that dolutegravir did not worsen neurocognitive performance. Other approaches will be needed to help people living with HIV with neurocognitive impairment.

Scott L Letendre and others, Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus, Clinical Infectious Diseases, 2023;, ciad265,