Abstract
ObjectiveTo assess the efficacy and safety of transdermal rivastigmine for the treatment of HIV-associated cognitive impairment.MethodsWe 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.ResultsSeventy-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.ConclusionsThe 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.
Highlights
Better cognitive outcomes were observed in all groups, there were no significant differences between the arms: rivastigmine, 0.35 (0.14); lithium, 0.25 (0.40); control, 0.20 (0.44) (p = 0.78)
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 HIV-associated neurocognitive disorders (HAND) on stable antiretroviral therapy, even though positive trends were found in specific cognitive domains
Cognitive impairment has become a persistent complication in people with HIV infection, despite the use of combination antiretroviral therapy
Summary
Cognitive impairment has become a persistent complication in people with HIV infection, despite the use of combination antiretroviral therapy (cART). Rivastigmine halts the action of the enzyme acetylcholinesterase, increasing levels of acetylcholine in the brain and enhancing the function of neural cells, those involved in attention and working memory processes [9]. This drug has beneficial non-cholinergic effects, including Aβ brain load reduction and neuroprotective and anti-inflammatory effects in vivo and in vitro [10,11]. Both animal and human studies have demonstrated that Aβ metabolism can be altered by HIV infection [12,13]. The only compound that has proven beneficial is lithium; its benefits appear to be variable, and the incidence of adverse events, hypothyroidism, diabetes insipidus, and lithium toxicity, is high [15,16]
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