Minocycline treatment for HIV-associated cognitive impairment

Results from a randomized trial

Ned Sacktor, S. Miyahara, L. Deng, S. Evans, G. Schifitto, B. A. Cohen, R. Paul, K. Robertson, B. Jarocki, K. Scarsi, R. W. Coombs, Mary Christine Zink, A. Nath, E. Smith, R. J. Ellis, E. Singer, J. Weihe, S. McCarthy, L. Hosey, D. B. Clifford

Research output: Contribution to journalArticle

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 100mgor 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.

Original languageEnglish (US)
Pages (from-to)1135-1142
Number of pages8
JournalNeurology
Volume77
Issue number12
DOIs
StatePublished - Sep 20 2011

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Minocycline
HIV
Placebos
Safety
HIV-1
Therapeutics
Clinical Trials Data Monitoring Committees
Outcome Assessment (Health Care)
Medical Futility
Neuropsychological Tests
Cognitive Dysfunction
Cognitive Impairment
AIDS/HIV
Confidence Intervals
Placebo
Efficacy

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Sacktor, N., Miyahara, S., Deng, L., Evans, S., Schifitto, G., Cohen, B. A., ... Clifford, D. B. (2011). Minocycline treatment for HIV-associated cognitive impairment: Results from a randomized trial. Neurology, 77(12), 1135-1142. https://doi.org/10.1212/WNL.0b013e31822f0412

Minocycline treatment for HIV-associated cognitive impairment : Results from a randomized trial. / Sacktor, Ned; Miyahara, S.; Deng, L.; Evans, S.; Schifitto, G.; Cohen, B. A.; Paul, R.; Robertson, K.; Jarocki, B.; Scarsi, K.; Coombs, R. W.; Zink, Mary Christine; Nath, A.; Smith, E.; Ellis, R. J.; Singer, E.; Weihe, J.; McCarthy, S.; Hosey, L.; Clifford, D. B.

In: Neurology, Vol. 77, No. 12, 20.09.2011, p. 1135-1142.

Research output: Contribution to journalArticle

Sacktor, 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 2011, 'Minocycline treatment for HIV-associated cognitive impairment: Results from a randomized trial', Neurology, vol. 77, no. 12, pp. 1135-1142. https://doi.org/10.1212/WNL.0b013e31822f0412
Sacktor, Ned ; Miyahara, S. ; Deng, L. ; Evans, S. ; Schifitto, G. ; Cohen, B. A. ; Paul, R. ; Robertson, K. ; Jarocki, B. ; Scarsi, K. ; Coombs, R. W. ; Zink, Mary Christine ; Nath, A. ; Smith, E. ; Ellis, R. J. ; Singer, E. ; Weihe, J. ; McCarthy, S. ; Hosey, L. ; Clifford, D. B. / Minocycline treatment for HIV-associated cognitive impairment : Results from a randomized trial. In: Neurology. 2011 ; Vol. 77, No. 12. pp. 1135-1142.
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AU - Nath, A.

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N2 - 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 100mgor 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.

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