Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment.

TitleImpact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment.
Publication TypeJournal Article
Year of Publication2014
AuthorsSacktor N, Miyahara S, Evans S, Schifitto G, Cohen B, Haughey N, Drewes JL, Graham D, M Zink C, Anderson C, Nath A, Pardo CA, McCarthy S, Hosey L, Clifford D
Corporate AuthorsACTG A5235 team
JournalJ Neurovirol
Volume20
Issue6
Pagination620-6
Date Published2014 Dec
ISSN1538-2443
KeywordsAcquired Immunodeficiency Syndrome, Administration, Oral, Adult, AIDS Dementia Complex, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Ceramides, Cytokines, Double-Blind Method, Female, Glutamic Acid, HIV-1, Humans, Kynurenine, Male, Middle Aged, Minocycline, Neurofilament Proteins, Neurons, Neuroprotective Agents, Nitric Oxide Synthase Type II, Oxidative Stress
Abstract

Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, "Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment," minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), glutamate, neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers.These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results.

DOI10.1007/s13365-014-0292-0
Alternate JournalJ. Neurovirol.
PubMed ID25377444
PubMed Central IDPMC4268406
Grant ListAI 068634 / AI / NIAID NIH HHS / United States
AI 127757 / AI / NIAID NIH HHS / United States
AI046376 / AI / NIAID NIH HHS / United States
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MH075673 / MH / NIMH NIH HHS / United States
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