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

PLOS ONE, Nov 2019

Objective To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment. Methods 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. 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. Conclusions 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.

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

August Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study Jose A. Muñoz-Moreno 0 1 Anna Prats 0 1 Jose Molto 0 1 Maite Garolera 1 Nu ria Pe rez- A lvarez 0 1 Crisanto DÂõez-Quevedo 1 Cristina Miranda 0 1 Carmina R. Fumaz 0 1 Maria J. Ferrer 0 1 Bonaventura Clotet 0 1 on behalf of the TRIANT-TE Study Group 1 0 Fundaci o Lluita contra la SIDA (FLS), Hospital Universitari Germans Trias i Pujol , Badalona, Catalonia , Spain , 2 Facultat de Psicologia i Ciències de l'Educacio , Universitat Oberta de Catalunya (UOC) , Barcelona, Catalonia , Spain , 3 Departament de Psiquiatria i Medicina Legal, Universitat Autònoma de Barcelona (UAB) , Cerdanyola del Vallès, Catalonia , Spain , 4 Clinical Research Group for Brain, Cognition and Behavior, Consorci Sanitari Hospital de Terrassa , Terrassa, Catalonia , Spain , 5 Grup de Recerca Consolidat en Neuropsicologia, Universitat de Barcelona (UB) , Barcelona, Catalonia, Spain, 6 Departament d'EstadÂõstica i Investigacio Operativa , Universitat Politècnica de Catalunya (UPC) , Barcelona, Catalonia, Spain, 7 Servei de Psiquiatria , Hospital Universitari Germans Trias i Pujol , Badalona, Catalonia, Spain, 8 Institut per la Recerca de la SIDA IrsiCaixa, Badalona, Catalonia, Spain, 9 Càtedra de la SIDA i Malalties Relacionades , Universitat de VicÐUniversitat Central de Catalunya (UVic) , Vic, Catalonia , Spain 1 Editor: Alan Winston, Imperial College London , UNITED KINGDOM - Funding: The study was supported by the Spanish Ministry of Health and Social Policy as part of the 2010 Call for Clinical Independent Investigation Projects (project code: EC10-320), and by a grant from the Lluita contra la SIDA Foundation (project code: B-904). Competing interests: The authors have declared that no competing interests exist. Objective ciated cognitive impairment. Methods To assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-asso 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. 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. Conclusions 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. Introduction Cognitive impairment has become a persistent complication in people with HIV infection, despite the use of combination antiretroviral therapy (cART). Reports show a prevalence of between 30% and 60% in people living with HIV during the recent cART era [ 1,2 ], and this impairment appears to have a negative effect on quality of life [3], daily functioning [ 4 ], and clinical outcomes (e.g., poor adherence to antiretroviral therapy and frequent virological failure) [ 5,6 ]. Adjuvant pharmacological therapies have been suggested for the management of HIV-associated neurocognitive disorders (HAND), although most trials investigating them have not proved clear benefits [7]. Rivastigmine is a cholinesterase inhibitor used to treat cognitive impairment, mainly in Alzheimer's and Parkinson's diseases [ 8 ]. Rivastigmine halts the action of the enzyme acetylcholinesterase, thus increasing levels (...truncated)


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Jose A. Muñoz-Moreno, Anna Prats, José Moltó, Maite Garolera, Núria Pérez-Álvarez, Crisanto Díez-Quevedo, Cristina Miranda, Carmina R. Fumaz, Maria J. Ferrer, Bonaventura Clotet, on behalf of the TRIANT-TE Study Group. Transdermal rivastigmine for HIV-associated cognitive impairment: A randomized pilot study, PLOS ONE, 2017, Volume 12, Issue 8, DOI: 10.1371/journal.pone.0182547