Journal Article

Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study

Ferrer, Maria J., Pérez-Álvarez, Núria, Prats, Anna, Moltó, José, Garolera, Maite, Miranda, Cristina, Díez-Quevedo, Crisanto, Fumaz, Carmina R., Muñoz-Moreno, Jose A., Clotet, Bonaventura

2017

Overview

To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment. We recruited HIV-infected patients with cognitive impairment on stable antiretroviral therapy in a randomized controlled pilot trial with a 48-week follow-up. An additional assessment was held at 12 weeks. Participants received transdermal rivastigmine (9.5 mg daily), lithium (400 mg twice daily, titrated progressively), or remained in a control group (no new medication). The primary efficacy endpoint was change in a global cognitive score (NPZ-7). Secondary endpoints included change in specific cognitive measures, domains, and functional parameters. Safety covered the frequency of adverse events and changes in laboratory results. Seventy-six subjects were screened, and 29 were finally enrolled. Better cognitive outcomes were observed in all groups, although there were no significant differences between the arms (mean NPZ-7 change [SD]): rivastigmine, 0.35 (0.14); lithium, 0.25 (0.40); control, 0.20 (0.44) (p = 0.78). The rivastigmine group showed the highest positive trend (mean NPZ-7 [SD], baseline vs week 48): rivastigmine, -0.47 (0.22) vs -0.11 (0.29), p = 0.06; lithium, -0.50 (0.40) vs -0.26 (0.21), p = 0.22; control, -0.52 (0.34) vs -0.32 (0.52), p = 0.44. The cognitive domains with the highest positive trends were information processing speed at week 12 and executive function at week 48 (rivastigmine vs control): information processing speed, 0.35 (0.64) vs -0.13 (0.25), p = 0.17, d = 0.96; and executive functioning, 0.73 (0.33) vs 0.03 (0.74), p = 0.09, d = 1.18. No relevant changes were observed regarding functional outcomes. A total of 12 (41%) individuals dropped out of the study: 2 (20%) were due to medication-related effects in the rivastigmine group and 4 (36%) in the lithium group. No severe adverse events were reported. The results from this small randomized trial indicate that transdermal rivastigmine did not provide significant cognitive benefits in people with HAND on stable antiretroviral therapy, even though positive trends were found in specific cognitive domains. Relevant tolerability issues were not observed.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Administration, Cutaneous / Adult / AIDS / Anti-Retroviral Agents - therapeutic use / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / Biology and Life Sciences / Cognitive ability / Cognitive disorders / Cognitive Dysfunction - drug therapy / Cognitive Dysfunction - etiology / Cognitive Dysfunction - virology / Complications and side effects / Computer and Information Sciences / Data processing / Dementia / Dosage and administration / Drug therapy / Drugs / Executive function / Executive Function - drug effects / Female / HIV / HIV infections / HIV Infections - complications / HIV Infections - drug therapy / Hospitals / Human immunodeficiency virus / Humans / Impairment / Infections / Information processing / Lithium / Lithium - therapeutic use / Male / Medical diagnosis / Medicine and Health Sciences / Middle Aged / Neuroprotective Agents - administration & dosage / Neuroprotective Agents - adverse effects / Neuroprotective Agents - therapeutic use / Neuropsychological Tests / Neuropsychology / Parkinson's disease / Physical Sciences / Pilot Projects / Psychological aspects / Research and Analysis Methods / Risk factors / Rivastigmine / Rivastigmine - administration & dosage / Rivastigmine - adverse effects / Rivastigmine - therapeutic use / Safety / Studies / Therapy / Treatment Outcome / Trends