A Placebo Controlled Trial of Baricitinib in People on ART to Reduce CNS HIV
William Tyor1, David Loring6, Taylor Harrison7, Minh Nguyen2, Ryan Peterson5, Kaundinya Gopinath3, Howard Pope5, Ali Alvarez5, Kirk Easley8, Vincent Marconi2, Christina Gavegnano4, Candace Fleischer3
1Neurology, 2Medicine, 3Radiology, 4Pathology, Emory University School of Medicine, 5Emory University School of Medicine, 6Emory Univ, Dept of Neurology, 7Neurology, Emory University, 8Emory University
Objective:
Reduce CSF HIV in people with HIV (PWH).
Background:
While antiretroviral treatment (ART) has reduced the severity of HIV cognitive impairment (HIV CI), brain remains a reservoir for HIV and mild HIV CI is common. HIV and neuroinflammation are drivers of HIV CI. Baricitinib, a JAK 1/2 inhibitor, has been shown to reduce the HIV macrophage reservoir in vitro and in a mouse HIV CI model. Baricitinib also reduced HIV-induced inflammation in mouse brains. These studies prompted a clinical trial in PWH virally controlled on ART.
Design/Methods:
64 PWH (18-65) on ART will be randomized to 2 mg daily of baricitinib or placebo given orally for 10 weeks. The primary endpoint is CSF HIV viral load with secondary endpoints including CSF and blood biomarkers (eg, IL-6), extensive neuropsychological testing, and 7T MRI including MR spectroscopy (MRS), collected before randomization and after 10 weeks of treatment. So far, correlations between baseline (prior to randomization) selected MRS and neuropsychological tests were analyzed for 20 participants.
Results:
So far, 21 participants have been randomized and 19 completed the study. The average age is 49, 42% are female, and 95% identify as Black. Increased myoinositol/creatine (mI/Cr) ratios in left frontal white matter correlated with decreased Digit Symbol Modalities Test scores (r=0.4415, p=0.051) and increased Trail Making Part B scores (r=0.496, p=0.026).
Conclusions:
Preliminary baseline analyses demonstrate increased glial reaction in frontal white matter correlates with worsening cognitive test scores in PWH. Baseline data will be presented in a larger group of PWH including correlations between 7T MRI parameters, neuropsychological testing and a broad spectrum of serum and CSF biomarkers. We predict this data will provide important information characterizing brain imaging, cognitive function and systemic and CNS immunological parameters in our baseline study population randomized to a JAK inhibitor vs placebo to ultimately determine CNS HIV reduction in PWH.
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