Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment: results from a double-blind, placebo-controlled trial View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-02

AUTHORS

Ned Sacktor, Richard L. Skolasky, Richard Moxley, Sheng Wang, Michelle M. Mielke, Cynthia Munro, Joseph Steiner, Avindra Nath, Norman Haughey, Justin McArthur

ABSTRACT

Paroxetine and fluconazole have neuroprotective effects in an in vitro model of HIV protein-mediated neuronal injury. This study evaluated the safety, tolerability, and efficacy of both paroxetine and fluconazole for the treatment of HIV-associated neurocognitive disorder (HAND). A 24-week randomized double-blind, placebo-controlled 2 × 2 factorial design study was used. HIV+ individuals with cognitive impairment were enrolled in the 24-week trial. Participants were randomly assigned to one of four groups: (1) paroxetine 20 mg/day, (2) fluconazole 100 mg every 12 h, (3) paroxetine and fluconazole, or (4) placebo. Safety, tolerability, and efficacy were evaluated. Forty-five HIV+ individuals were enrolled. Medications were well tolerated. Compared to no paroxetine arms, HIV+ individuals receiving paroxetine showed improved NPZ8 summary scores, (mean change = 0.25 vs - 0.19, p = 0.049), CalCAP sequential test reaction time (mean change = 0.34 vs -0.23, p = 0.014), Trail Making Part B test performance (mean change = 0.49 vs - 0.33, p = 0.041), and FAS verbal fluency (mean change = 0.25 vs 0.02, p = 0.020) but a decline in the Letter number sequencing test (mean change = - 0.40 vs 0.26, p = 0.023). Biomarkers of cellular stress, inflammation, and neuronal damage were not affected by paroxetine. HIV+ individuals receiving fluconazole did not show a benefit in cognition and showed an increase in multiple markers of cellular stress compared to the no fluconazole arms. In conclusion, paroxetine was associated with improvement in a summary neuropsychological test measure and in several neuropsychological tests but worse performance in one neuropsychological test. Further studies of paroxetine for the treatment of HAND and to define its precise neuroprotective properties are warranted. More... »

PAGES

16-27

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13365-017-0587-z

DOI

http://dx.doi.org/10.1007/s13365-017-0587-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092336063

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29063516


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246 https://www.grid.ac/institutes/grid.94365.3d schema:alternateName National Institutes of Health
247 schema:name National Institutes of Health, Bethesda, MD, USA
248 rdf:type schema:Organization
 




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