Effect of aprepitant on kynurenine to tryptophan ratio in cART treated and cART naïve adults living with HIV
| Autor: | Annemarie Kinder, Jay Rappaport, Dwight L. Evans, Steven D. Douglas, Sergei Spitsin, Vasiliki Pappa |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Cart Anti-HIV Agents Neuroimmunomodulation substance P Observational Study HIV Infections Pharmacology Placebo 03 medical and health sciences chemistry.chemical_compound neurokinin-1 0302 clinical medicine Pharmacotherapy Double-Blind Method Neurokinin-1 Receptor Antagonists Humans Medicine tryptophan 030212 general & internal medicine tachykinins Kynurenine Aprepitant aprepitant Ritonavir Mood Disorders business.industry Antagonist HIV virus diseases General Medicine medicine.disease CD4 Lymphocyte Count Regimen Treatment Outcome chemistry Mood disorders 030220 oncology & carcinogenesis Drug Therapy Combination Female business Research Article medicine.drug |
| Zdroj: | Medicine |
| ISSN: | 1536-5964 0025-7974 |
| Popis: | Changes in tryptophan metabolism affect human physiology including the immune system, mood, and sleep and are associated with human immunodeficiency virus (HIV) pathogenesis. This study investigates whether the treatment of HIV-infected individuals with the neurokinin-1 receptor antagonist, aprepitant, alters tryptophan metabolism. This study utilized archival samples from 3 phase 1B clinical trials “Anti-HIV Neuroimmunomodulatory Therapy with Neurokinin-1 Antagonist Aprepitant”-2 double-blinded, placebo-controlled, and 1 open-label study. We tested samples from a total of 57 individuals: 26 combination antiretroviral therapy (cART) naïve individuals receiving aprepitant, 19 cART naïve individuals receiving placebo, and 12 individuals on a ritonavir-containing cART regimen receiving aprepitant. We evaluated the effect of aprepitant on tryptophan metabolism by measuring levels of kynurenine and tryptophan in archival plasma samples and calculating the kynurenine to tryptophan ratio. Aprepitant treatment affected tryptophan metabolism in both cART treated and cART naïve individuals with more profound effects in patients receiving cART. While aprepitant treatment affected tryptophan metabolism in all HIV-infected patients, it only significantly decreased kynurenine to tryptophan ratio in cART treated individuals. Aprepitant treatment offers an opportunity to target inflammation and mood disorders frequently co-existing in chronic HIV infection. |
| Databáze: | OpenAIRE |
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