Moderate to severe HIV-associated neurocognitive impairment : a randomized placebo-controlled trial of lithium

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dc.contributor.authorDecloedt, Eric H.en_ZA
dc.contributor.authorFreeman, Carlaen_ZA
dc.contributor.authorHowells, Fleuren_ZA
dc.contributor.authorCasson-Crook, Martineen_ZA
dc.contributor.authorLesosky, Maiaen_ZA
dc.contributor.authorKoutsilieri, Elenien_ZA
dc.contributor.authorLovestone, Simonen_ZA
dc.contributor.authorMaartens, Garyen_ZA
dc.contributor.authorJoska, John A.en_ZA
dc.date.accessioned2017-07-18T07:17:23Z
dc.date.available2017-07-18T07:17:23Z
dc.date.issued2016-11
dc.descriptionCITATION: Decloedt, E. H. et al. 2016. Moderate to severe HIV-associated neurocognitive impairment : a randomized placebo-controlled trial of lithium. Medicine, 95(46):e5401, doi:10.1097/MD.0000000000005401.
dc.descriptionThe original publication is available at http://journals.lww.com/md-journal
dc.description.abstractBackground: 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. Methods: 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 (1H-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. Results: 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 1H-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. Conclusion: Adjunctive lithium pharmacotherapy in patients on ART with HAND was well tolerated but had no additional benefit on neurocognitive impairment.en_ZA
dc.description.urihttp://journals.lww.com/md-journal/Fulltext/2016/11150/Moderate_to_severe_HIV_associated_neurocognitive.50.aspx
dc.description.versionPublisher's version
dc.format.extent7 pages
dc.identifier.citationDecloedt, E. H. et al. 2016. Moderate to severe HIV-associated neurocognitive impairment : a randomized placebo-controlled trial of lithium. Medicine, 95(46):e5401, doi:10.1097/MD.0000000000005401.
dc.identifier.issn1536-5964 (online)
dc.identifier.otherdoi:10.1097/MD.0000000000005401
dc.identifier.urihttp://hdl.handle.net/10019.1/101988
dc.language.isoen_ZAen_ZA
dc.publisherWolters Kluwer Health
dc.rights.holderAuthors retain copyright
dc.subjectLithiumen_ZA
dc.subjectHIV infectionsen_ZA
dc.subjectAntiretroviral therapyen_ZA
dc.subjectNervous system -- Diseasesen_ZA
dc.titleModerate to severe HIV-associated neurocognitive impairment : a randomized placebo-controlled trial of lithiumen_ZA
dc.typeArticleen_ZA
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