A5324: To see if adding extra anti-HIV medicines reduces HIV-associated neurocognitive disorder


 Protocol Summary: hiv-related-brain-damage-hand

This is a phase IV randomized, double-blinded, placebo-controlled study to assess the efficacy of adding maraviroc (MVC) and dolutegravir (DTG) to the current antiretroviral therapy (ART) of HIV-infected individuals who have at least mild neurocognitive impairment with a primary outcome of improvement in neurocognitive performance.

Purpose of This Study:

Objectives of this study are:

  • To assess the safety and tolerability of MVC and DTG when added to a stable ART regimen;

  • To determine if intensification with MVC and DTG, or DTG alone, will improve neurocognitive functioning at week 48 in subjects who have at least mild neurocognitive impairment;

  • To determine the effect of MVC and/or DTG, on biomarkers in the blood and CSF

Requirements to Enter study:

  • HIV+ adults, age 18+
  • On current ART >12 mos, with no plans to change while on study; no prior or current use of MVC or any integrase inhibitor; no current use of nevirapine, tripranavir, fosampranavir.
  • HIV-1 RNA <50 copies/mL within 90 days prior to study entry; only one ‘blip’ <200 copies/mL
  • allowed in the past 6 months.
  • HAND diagnosis (ANI, MND, or HAD) determined at screening clinical visit.
  • Women of reproductive potential at least one reliable method of contraception throughout study.
  • No current or past medical condition(s) that in the opinion of the investigator prevents attribution of
  • cognitive impairment to HIV. Examples: major depressive disorder with psychotic features;
  • traumatic brain injury; mental retardation/severe educational disability; ongoing substance use
  • disorder with significant impact on daily living activities; CNS infections/conditions.
  • No known untreated B12 deficiency or malnutrition
  • No Hepatitis C virus seropositive/unstable and advanced liver disease
  • No presence of an AIDS-defining opportunistic infection within 180 days
  • No active syphilis or treatment for syphilis within 90 days

Treatment:

Randomized (1:1:1) at entry to:

  • Arm A: placebo for MVC and placebo for DTG
  • Arm B: DTG and placebo for MVC
  • Arm C: MVC and DTG

Neuropsychological testing will be done at entry and every 24 weeks.

Duration of Study:

Subjects will participate in this study for 96 weeks. There are 10 clinic visits, including screening and pre-entry visits. Compensation and parking/bus tickets provided. Travel reimbursement expenses are provided.