TY - JOUR
T1 - Minocycline treatment for HIV-associated cognitive impairment
T2 - Results from a randomized trial
AU - Sacktor, N.
AU - Miyahara, S.
AU - Deng, L.
AU - Evans, S.
AU - Schifitto, G.
AU - Cohen, B. A.
AU - Paul, R.
AU - Robertson, K.
AU - Jarocki, B.
AU - Scarsi, K.
AU - Coombs, R. W.
AU - Zink, M. C.
AU - Nath, A.
AU - Smith, E.
AU - Ellis, R. J.
AU - Singer, E.
AU - Weihe, J.
AU - McCarthy, S.
AU - Hosey, L.
AU - Clifford, D. B.
N1 - Funding Information:
Supported in part by the AIDS Clinical Trials Group (ACTG) (full protocol available from the ACTG upon request) funded by: NIAID, AI38858, AI38855, AI27670, AI27668, AI27658, AI34853, AI127660, AI27664, AI27659, AI25903, AI25915, AI046376, AI46370, AI46381, AI50410, AI25868, AI46386, CFAR AI 127757 , the Neurologic AIDS Research Consortium , NS32228 , the National Institute of Mental Health , MH71150, MH64409, AI 068634 , and GCRC Units funded by the National Center for Research Resources (NCRR) , RR00052, RR00044, RR00046 . The NCT number for this study is NCT 00361257 . This study is registered in ClinicalTrials.gov . Participating site ACTG Clinical Trials Unit (CTU) grant numbers include the following: University of California, San Diego Antiviral Research CTU Grant AI069432 , Johns Hopkins University CTU Grant AI069465 , CTSA Grant UL1 RR025005 , UCLA School of Medicine CTU Grant AI069424 , Washington University (St. Louis) CTU Grant AI069495 , The Research & Education Group-Portland CRS CTU Grant AI069503 , Henry Ford Hospital CRS CTU Grant AI069503 , Massachusetts General Hospital CTU Grant AI069472 , NYU/NYC HHC at Bellevue CTU Grant AI069532 , University of Colorado Hospital CTU Grant AI069450 , Northwestern University CTU Grant AI069471 , Virginia Commonwealth University Medical Center CRS CTU Grant AI069503 , University of Washington (Seattle) CTU Grant AI069434 , University of North Carolina CTU Grant AI069423 , University of Rochester Medical Center CTU Grant AI069511 , Emory University, The Ponce de Leon Center CTU Grant AI069452 , University of Pennsylvania, Philadelphia CTU Grant AI069467–04 . Manufacture of the minocycline and matching placebo was funded with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract no. N01-AI-05414 . The project described was supported by Award AI068636 from the National Institute of Allergy and Infectious Diseases , National Institute of Mental Health (NIMH), and National Institute of Dental and Craniofacial Research (NIDCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.
PY - 2011/9/20
Y1 - 2011/9/20
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80555157650&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e31822f0412
DO - 10.1212/WNL.0b013e31822f0412
M3 - Article
C2 - 21900636
AN - SCOPUS:80555157650
SN - 0028-3878
VL - 77
SP - 1135
EP - 1142
JO - Neurology
JF - Neurology
IS - 12
ER -