Efficacy and Safety of Two Pharmacologic Strategies on Neurocognitive Impairment in HIV Infection. The TRIANT-TE Study
Condition: Neurocognitive Disturbance; HIV Infection
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 4

Summary: 
      The current project proposes the comparison of two pharmacologic strategies as adjunctive
      treatments for the improvement of HIV-associated neurocognitive disruption, additionally to
      use of HAART. The investigators propose the use of the compound that has shown greatest
      benefits in this context to date, the lithium, versus the use of a well-tolerated and
      promising drug in other pathologies with neurocognitive affectation, such as Alzheimer or
      Parkinson diseases, which is the rivastigmine. In those other diseases, this second compound
      has recently offered a good tolerability, but also benefits on attention, memory and other
      neurocognitive areas. Both study groups, patients on therapy with lithium and patients on
      therapy with rivastigmine, will be compared to a control group, which will not initiate any
      other treatment (therefore only continuing antiretroviral therapy). The investigators are
      aware that this proposal will offer new relevant data for the study of neurocognitive
      improvement in HIV infection, as well will allow a better knowledge of clinical management of
      HIV-infected patients with CNS disease, an aspect that is a common clinical concern today.
    

Detailed description: 
      Adjunctive treatments based on neurocognitive improvement for HIV-infected patients with CNS
      disruption have consisted essentially of neurostimulant or neuroprotective treatments.
      Reports published to date have involved valproic acid, peptide T, CPI-1189, selegiline,
      memantine, minocycline and lithium. Regarding valproic acid, two trials have confirmed lack
      of benefit using this compound on HIV-associated neurocognitive decline. In case of peptide
      T, CPI-1189, selegiline, memantine and minocycline, although their potential mechanisms on
      brain follow different pathways, trend towards improvement on neurocognitive functioning has
      been observed. Nonetheless, results on those trials are particularly based on a short term
      and, moreover, mild connections with benefits on neurocognitive and functional measures have
      been established. The lithium has been the compound showing clearest benefits on this regard.
      Two reports have consistently demonstrated benefits on neurocognitive performance using this
      neuroprotective agent, both in patients with HIV and showing impairment previously. However,
      lithium is well known to be a drug not easily incorporated in routine practice, at least
      further than in a psychiatry context. In addition, adverse events related to their use are
      relatively frequent, and therefore clinical follow-up must be especially controlled. Besides,
      lithium concentrations are also a concerning aspect considering its use, and drug plasma
      levels are recommended to be performed throughout the therapy application.

      For all these reasons, the current project proposes the comparison of two pharmacologic
      strategies as adjunctive treatments for the improvement of HIV-associated neurocognitive
      disruption, additionally to use of HAART. The investigators propose the use of the compound
      that has shown greatest benefits in this context to date, the lithium, versus the use of a
      well-tolerated and promising drug in other pathologies with neurocognitive affectation, such
      as Alzheimer or Parkinson diseases, which is the rivastigmine. In those other diseases, this
      second compound has recently offered a good tolerability, but also benefits on attention,
      memory and other neurocognitive areas. Furthermore, in the case of this project, rivastigmine
      is suggested to be used through a transdermal system patch, a fact that can provide
      suitability and comfortability with regard to the selected administration method. Both study
      groups, patients on therapy with lithium and patients on therapy with rivastigmine, will be
      compared to a control group, which will not initiate any other treatment (therefore only
      continuing antiretroviral therapy). The investigators are aware that this proposal will offer
      new relevant data for the study of neurocognitive improvement in HIV infection, as well will
      allow a better knowledge of clinical management of HIV-infected patients with CNS disease, an
      aspect that is a common clinical concern today.
    

Intervention name(s): Lithium; Rivastigmine
Intervention type(s): Drug; Drug
Intervention description(s): lithium, in tablets, beginning a 2-daily 400 mg dose, and changing further adjusting the dose according to drug levels in serum.; rivastigmine, in transdermal patch administration, beginning a once-daily 4.6 mg dose, and changing further increasing the dose up to once-daily 9.5 mg.
Intervention MeSH terms: Rivastigmine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Neurocognitive Impairment; Controlled Randomized Trial; Coadjunctive Treatments; Lithium; Rivastigmine; Antiretroviral Therapy; HIV Infection