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HIV-associated neurocognitive disorder (HAND) remains highly prevalent despite effective anti-retroviral therapy (ART). A number of adjunctive pharmacotherapies for HAND have been studied with disappointing results, but preliminary data suggest that lithium may provide clinical benefit. In addition, the low cost of lithium would facilitate access in low- and middle-income countries which carry the greatest burden of HIV.Our objective was to evaluate the 24-week efficacy and safety of lithium in patients with moderate to severe HAND. Our primary efficacy endpoint was the change in Global Deficit Score (GDS) from baseline to 24 weeks, whereas our secondary endpoint was the change in proton magnetic resonance spectroscopy (H-MRS) brain metabolite concentrations. We conducted a 24-week randomized placebo-controlled trial of lithium as adjunctive pharmacotherapy. We enrolled participants with moderate to severe HAND, on ART for at least 6 months, with suppressed viral loads and attending public sector primary care clinics in Cape Town, South Africa. We randomized 66 participants to lithium (n = 32) or placebo (n = 34). Lithium or placebo was dosed 12-hourly and titrated to achieve the maintenance target plasma concentration of 0.6 to 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo.Totally 61 participants completed the study (lithium arm = 30; placebo arm = 31). Participants at enrolment had a mean age of 40 years and a median CD4+ T-cell count of 500 cells/μL. The median change in GDS between baseline and week 24 for the lithium and placebo arms were -0.57 (95% confidence interval [CI] -0.77, -0.32) and -0.56 (-0.69, -0.34) respectively, with a mean difference of -0.054 (95% CI -0.26, 0.15); P = 0.716. The improvement remained similar when analyzed according to age, severity of impairment, CD4+ count, time on ART, and ART regimen. Standard H-MRS metabolite concentrations were similar between the treatment arms. The study drug was well tolerated in both study arms. Six serious adverse events occurred, but none were considered related to the study drug.Adjunctive lithium pharmacotherapy in patients on ART with HAND was well tolerated but had no additional benefit on neurocognitive impairment.

Original publication

DOI

10.1097/md.0000000000005401

Type

Journal article

Journal

Medicine

Publication Date

11/2016

Volume

95

Pages

e5401 - e5401

Addresses

aDivision of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University bDivision of Neuropsychiatry, Department of Psychiatry and Mental Health, Faculty of Health Sciences cDivision of Epidemiology and Biostatistics, School of Public Health and Family Medicine dDivision of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa eDepartment of Psychiatry, University of Oxford, United Kingdom fInstitute of Virology and Immunobiology, University of Würzburg, Germany gDepartment of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.

Keywords

Brain, Humans, HIV Infections, Lithium Compounds, Psychotropic Drugs, Drug Monitoring, CD4 Lymphocyte Count, Treatment Outcome, Severity of Illness Index, Neuropsychological Tests, Adult, Middle Aged, Female, Male, Proton Magnetic Resonance Spectroscopy, Neurocognitive Disorders