Minocycline treatment for HIV-associated cognitive impairment

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 ϭ 0.12) compared to placebo (mean 24-week change ϭ 0.17) (95% confidence interval ϭ [Ϫ0.26, 0.39], p ϭ 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group.

Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment

“…These results are consistent with a second trial of minocycline for the treatment of HIVassociated cognitive impairment recently performed in HIV-positive individuals with neurocognitive impairment on cART. 15 Cognitive impairment as seen in the study population continues to be an important manifestation of HIV infection, affecting 40% to 60% of HIV seropositive individuals even after the initiation of highly active antiretroviral therapy. 19 The cognitive impairment observed in this particular study group could also have been due to non-HIV comorbid infections or conditions.…”

“…In contrast to a prior study 15 in the United States in which all HIV-positive individuals were receiving cART, this study was conducted in HIV-positive individuals who were not eligible for ART in the Uganda setting. Thus, the direct effect of minocycline and placebo in the absence of ART was examined in this study.…”

Rivastigmine for HIV-associated neurocognitive disorders

“…DISCUSSION This pilot study suggests that a treatment of rivastigmine for 20 weeks improves psychomotor speed and, marginally, executive functioning Table 1 Baseline demographics and clinical characteristics Treatment arm 1 (rivastigmine-placebo) (n 5 9) 34 ) have already been studied in patients with HAND without convincing results. As a matter of fact, none of these compounds is currently recommended in practice.…”

Evidence-based perspectives on the implementation of screening for neurocognitive impairment in HIV

“…Trials of adjunctive pharmacological treatment, including minocycline, selegiline, valproate, rivastigmine, and lithium, [82][83][84][85][86] have not shown benefits in cognitive function in PLWH. It may be that the trials were underpowered or too short in duration to show benefit, or that too heterogeneous a group of patients was targeted.…”