Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial

Thela, Lindokuhle; Decloedt, Eric; Zetterberg, Henrik; Gisslén, Magnus; Lesosky, Maia; Gleich, Melanie; Koutsilieri, Eleni; Scheller, Carsten; Hye, Abdul; Joska, John

doi:10.1007/s13365-023-01116-4

Cited by 2 publications

(1 citation statement)

References 71 publications

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“…Pharmacological therapies including adjuvant therapies (particularly minocycline, selegeline, memantine) were reviewed in a 2021 book chapter and, essentially, evidence remains limited [38]. There have been recent randomized controlled trials of lithium, and B vitamins as adjuvant treatments in cART-treated PWHA, both of which were unsuccessful [39]. There is some evidence of higher Central Nervous System Penetrance Effectiveness (CPE) score of cART regimens showing protection against HAND but the clinical picture is complicated by neuropsychiatric side effects of these regimens [40].…”

Section: Interventional Approachesmentioning

confidence: 99%

Recent advances in HIV-associated neurocognitive disorders: a focus on older adults and sub-Saharan Africa

Paddick,

Mukaetova-Ladinska

2023

Current Opinion in Psychiatry

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Purpose of review We reviewed recent literature on prevalence and interventional approaches for cognitive impairment in the context of HIV infection alongside current controversies and challenges around its nomenclature, screening, and diagnosis. Recent findings Prevalence estimates for HIV-associated neurocognitive disorder (HAND) indicate that HAND remains highly prevalent despite combination antiretroviral treatment (cART) widely used. The available data are heterogeneous, particularly in sub-Saharan Africa (SSA) where recent reviews indicate substantial heterogeneity, wide prevalence estimates and lack of data from the majority SSA countries, despite them currently experiencing the greatest burden worldwide of both HIV and HAND. Several alternative approaches to diagnosis and classification of cognitive impairment in HIV have been published, taking into account changing clinical phenotypes. Summary Cognitive impairment remains a significant challenge in the care of people living with HIV despite advances in treatment. Ongoing controversies exist around nomenclature and classification, screening measures, and the phenotype and aetiology of observed impairments. Two current areas of research priority and focus include understanding current phenotypes of individuals living and ageing with treated HIV and differing levels of risk for HAND in these phenotypes, alongside the effects of commonly occurring comorbidities. The current evidence base for interventional approaches is limited, but growing. The most promising avenues appear to be multidisciplinary. These are currently focussed on high income settings rather than SSA where the majority of people living with HIV, and affected by cognitive impairment in the context of HIV, currently reside.

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Section: Interventional Approachesmentioning

confidence: 99%

Recent advances in HIV-associated neurocognitive disorders: a focus on older adults and sub-Saharan Africa

Paddick,

Mukaetova-Ladinska

2023

Current Opinion in Psychiatry

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Serum and CSF biomarkers in asymptomatic patients during primary HIV infection: a randomized study

Calcagno,

Cusato,

Cinque

et al. 2024

Brain

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It is debated whether central nervous system involvement begins during acute HIV infection in persons without meningitis/encephalitis and if specific antiretroviral drugs or combinations would be beneficial. Neurologically asymptomatic participants enrolled in a randomized and controlled study comparing three combination antiretroviral regimens (tenofovir alafenamide/emtricitabine plus dolutegravir, darunavir or both) during primary HIV infection were enrolled. Serum and cerebrospinal fluid (CSF) were collected at baseline, 12 and 48 (serum only) weeks after treatment initiation. Single Molecule Array was used to measure neurofilament light chain (NFL), total tau protein (Tau), Brain-Derived Neurotrophic Factor (BDNF), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase (UCH-L1). We assessed the longitudinal change in biomarkers over time as well as the change in the prevalence of serum NFL concentrations above previously published age-adjusted cut-offs (7 pg/mL if 5-18 years, 10 pg/mL if 18-51 years, 15 pg/mL if 51-61 years, 20 pg/mL if 61-70 years and 35 pg/mL if >70 years). Serum was available from 47 participants at all time points while CSF was in 13 and 7 participants (baseline/W12). We observed a significant direct serum-to-CSF correlation for NFL (rho = 0.692, p = 0.009), GFAP (rho = 0.659, p = 0.014) and BDNF (rho = 0.587, p = 0.045). Serum (rho = 0.560, p = 0.046) and CSF NFL (rho = 0.582, p = 0.037) concentrations were directly associated with CSF HIV RNA levels. We observed a significant decrease over time in serum NFL (p = 0.006) and GFAP (p = 0.006) but not in the other biomarkers. No significant difference was observed among the treatment arms. At baseline, serum and CSF age-adjusted NFL levels were above age-adjusted cut-offs in 23 (48.9%) and 4 participants (30.8%); considering serum NFL, this proportion was lower at weeks 12 (31.9%, p = 0.057) and 48 (27.7%, p = 0.13). A relevant proportion of neurologically asymptomatic participants had abnormal CSF and serum NFL levels during primary HIV infection. NFL and GFAP decreased in serum following combination antiretroviral therapy without significant differences among the treatment arms.

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Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial

Cited by 2 publications

References 71 publications

Recent advances in HIV-associated neurocognitive disorders: a focus on older adults and sub-Saharan Africa

Recent advances in HIV-associated neurocognitive disorders: a focus on older adults and sub-Saharan Africa

Serum and CSF biomarkers in asymptomatic patients during primary HIV infection: a randomized study

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