Minocycline treatment for HIV-associated cognitive impairment: results from a randomized trial.

TitleMinocycline treatment for HIV-associated cognitive impairment: results from a randomized trial.
Publication TypeJournal Article
Year of Publication2011
AuthorsSacktor N, Miyahara S, Deng L, Evans S, Schifitto G, Cohen BA, Paul R, Robertson K, Jarocki B, Scarsi K, Coombs RW, Zink MC, Nath A, Smith E, Ellis RJ, Singer E, Weihe J, McCarthy S, Hosey L, Clifford DB
Corporate AuthorsACTG A5235 team
JournalNeurology
Volume77
Issue12
Pagination1135-42
Date Published2011 Sep 20
ISSN1526-632X
KeywordsAdult, Cognition Disorders, Cohort Studies, Double-Blind Method, Female, Follow-Up Studies, HIV Infections, HIV-1, Humans, Male, Middle Aged, Minocycline, Treatment Outcome
Abstract

OBJECTIVE: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment.

METHODS: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100 mg or matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination.

RESULTS: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change = 0.12) compared to placebo (mean 24-week change = 0.17) (95% confidence interval = [-0.26, 0.39], p = 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group.

CONCLUSION: Minocycline was safe and well-tolerated in individuals with HIV-associated cognitive impairment, but cognitive improvement was not observed. Classification of evidence. This interventional study provides Class II evidence for the safety, tolerability, and efficacy of minocycline for the treatment of HIV-associated cognitive impairment.

DOI10.1212/WNL.0b013e31822f0412
Alternate JournalNeurology
PubMed ID21900636
PubMed Central IDPMC3174065
Grant ListAI 068634 / AI / NIAID NIH HHS / United States
AI046376 / AI / NIAID NIH HHS / United States
AI068636 / AI / NIAID NIH HHS / United States
AI069423 / AI / NIAID NIH HHS / United States
AI069424 / AI / NIAID NIH HHS / United States
AI069432 / AI / NIAID NIH HHS / United States
AI069434 / AI / NIAID NIH HHS / United States
AI069450 / AI / NIAID NIH HHS / United States
AI069452 / AI / NIAID NIH HHS / United States
AI069465 / AI / NIAID NIH HHS / United States
AI069467-04 / AI / NIAID NIH HHS / United States
AI069471 / AI / NIAID NIH HHS / United States
AI069472 / AI / NIAID NIH HHS / United States
AI069495 / AI / NIAID NIH HHS / United States
AI069503 / AI / NIAID NIH HHS / United States
AI069511 / AI / NIAID NIH HHS / United States
AI069532 / AI / NIAID NIH HHS / United States
AI127660 / AI / NIAID NIH HHS / United States
AI25868 / AI / NIAID NIH HHS / United States
AI25903 / AI / NIAID NIH HHS / United States
AI25915 / AI / NIAID NIH HHS / United States
AI27658 / AI / NIAID NIH HHS / United States
AI27659 / AI / NIAID NIH HHS / United States
AI27664 / AI / NIAID NIH HHS / United States
AI27668 / AI / NIAID NIH HHS / United States
AI27670 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI46381 / AI / NIAID NIH HHS / United States
AI46386 / AI / NIAID NIH HHS / United States
AI50410 / AI / NIAID NIH HHS / United States
MH64409 / MH / NIMH NIH HHS / United States
MH71150 / MH / NIMH NIH HHS / United States
N01-AI-05414 / AI / NIAID NIH HHS / United States
NS32228 / NS / NINDS NIH HHS / United States
RR00044 / RR / NCRR NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States
RR00052 / RR / NCRR NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States