HIV and Neurocognitive Disorders: Looking for Drugs that Decrease Inflammation

Up to half of people living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND), a neurological manifestation of HIV-1 infection. HAND appears to manifest pursuant to persistent central nervous system inflammation, anomalous macrophage activation, and increased oxidative stress.

Researchers are interested in finding therapies that are neuroprotective and have screened thousands of compounds that are commercially available. Two compounds/classes—fluconazole and selective serotonin reuptake inhibitors—seem to protect hippocampal neurons. Furthermore, previous screenings suggested that when given together, their actions may be synergistic.

Researchers from the Johns Hopkins University School of Medicine in Baltimore, MD, conducted a study of the paroxetine and fluconazole, including 45 adult PLWH experiencing HAND. Their results, published in the Journal of Neural Virology, indicate that paroxetine was able to improve some neuropsychological test measures, but fluconazole had little benefit.

Study participants were treated for 6 months in a design that ensured each participant was treated with paroxetine plus fluconazole, paroxetine alone, fluconazole alone, and placebo alone. The researchers found that study participants tolerated both drugs well and they identified few adverse reactions.

Participants treated with paroxetine improved on a number of neurocognitive parameters, but not all. The researchers noted that previously, more than 10 placebo-controlled trials looked at various drugs to treat HIV-associated cognitive impairment. None of the studies produced positive results, which lends significance to this study, the first in which a drug—paroxetine— showed some positive results.

Paroxetine is usually used to treat depression. Of note, participants in this study who were treated with paroxetine did not tend to have improved depression symptoms.

Participants treated with fluconazole did not show improvement in HAND and seemed to have measurable increases in cellular stress markers. However, circulating levels of 2 inflammatory cytokines did decrease. When given together, paroxetine and fluconazole did not seem to lead to any synergistic neurocognitive benefit.

This study, while small, indicates promise that drug treatment may help PLWH who develop neurocognitive deficits. The researchers noted that studies of longer duration would be prudent.

Even more neurology resources can be found on Pharmacy Times' new sister site, NeurologyLive.

Reference

Sacktor N, Skolasky RL, Moxley R, et al. Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment: results from a double-blind, placebo-controlled trial. J Neurovirol. 2018;24(1):16-27.