Pregnenolone is a neuroactive steroid that exhibits actions highly relevant to treating depression in people living with HIV. The investigators' recent human data suggest that neuroactive steroids are decreased in people living with HIV and depression. In addition, multiple groups have reported reductions in neuroactive steroids in people without HIV who have depression. A total of 120 people living with HIV on antiretroviral therapy with depression will be randomized to either pregnenolone or placebo (2 groups/90 participants receiving pregnenolone and 30 participants receiving placebo). Drug dosage will begin at 50 mg daily and incrementally increase to 500 mg daily within the first 4 weeks, with a stable 500 mg/day regimen for the final 4 weeks. Behavioral testing and blood draw will be performed at baseline, 2 weeks, 4 weeks and 8 weeks, while magnetic resonance spectroscopy, and task-based functional magnetic resonance imaging (MRI) will be conducted at 2 weeks and 8 weeks.~The investigators hypothesize that pregnenolone will be well-tolerated in people living with HIV and depression, and that this intervention may improve brain activity and reduce inflammation.
This study will determine the effects of pregnenolone on brain function, inflammation and depressive symptoms in people living with HIV who have depression. Participants in this study will receive a pill of either pregnenolone or placebo, and can stay on their current antidepression medications. Brain imaging and behavioral assessments will be performed during the study.