Changes in Cerebrospinal Fluid, Liver and Intima-media-thickness Biomarkers in Patients with HIV-associated Neurocognitive Disorders Randomized to a Less Neurotoxic Treatment Regimen.

HAND Neuromarkers Neurovirology Non-invasive tools PLWH

Journal

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
ISSN: 1557-1904
Titre abrégé: J Neuroimmune Pharmacol
Pays: United States
ID NLM: 101256586

Informations de publication

Date de publication:
31 Oct 2023
Historique:
received: 15 05 2023
accepted: 27 09 2023
medline: 31 10 2023
pubmed: 31 10 2023
entrez: 31 10 2023
Statut: aheadofprint

Résumé

The prevalence of neurocognitive impairment in people living with HIV is estimated between 30 and 50%. The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. Aim of the study was to measure the change in CSF biomarkers, Fibroscan and IMT measurements in PLWH with HAND randomized to a less neurotoxic regimen, or continuing their treatment. Adult patients with HAND were screened and enrolled if presenting no major resistance associated mutations, no HIV viral replication, not on efavirenz or darunavir, with R5-tropic HIV and without major confounding conditions. Lumbar puncture, IMT and Fibroscan measurements were performed. After 1:1 randomization to a less neurotoxic regimen consisting of darunavir/cobicistat plus emtricitabine plus maraviroc, or mantaining actual care, tests were repeated after 24 weeks: CSF biomarkes (HIV RNA, tau, p-tau, Beta-amyloid

Identifiants

pubmed: 37906406
doi: 10.1007/s11481-023-10086-7
pii: 10.1007/s11481-023-10086-7
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. The Author(s).

Références

Alford K, Daley S, Banerjee S et al (2021) Quality of life in people living with HIV-associated neurocognitive disorder: A scoping review study. Plos One 16(5):e0251944. https://doi.org/10.1371/journal.pone.0251944
Anderson AM, Easley KA, Kasher N et al (2018) Neurofilament light chain in blood is negatively associated with neuropsychological performance in HIV-infected adults and declines with initiation of antiretroviral therapy. J Neurovirol 24(6):695–701. https://doi.org/10.1007/s13365-018-0664-y
doi: 10.1007/s13365-018-0664-y pubmed: 30105502 pmcid: 6279552
Antinori A, Arendt G, Becker JT et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69(18):1789–1799. https://doi.org/10.1212/01.WNL.0000287431.88658.8b
doi: 10.1212/01.WNL.0000287431.88658.8b pubmed: 17914061
Bandera A, Taramasso L, Bozzi G et al (2019) HIV-Associated Neurocognitive Impairment in the Modern ART Era: Are We Close to Discovering Reliable Biomarkers in the Setting of Virological Suppression? Front Aging Neurosci 11:187. https://doi.org/10.3389/fnagi.2019.00187
doi: 10.3389/fnagi.2019.00187 pubmed: 31427955 pmcid: 6687760
Barco A, Orlando S, Stroffolini G et al (2022) Correlations between cerebrospinal fluid biomarkers, neurocognitive tests, and resting-state electroencephalography (rsEEG) in patients with HIV-associated neurocognitive disorders. J Neurovirol. https://doi.org/10.1007/s13365-021-01047-y
doi: 10.1007/s13365-021-01047-y pubmed: 35044644
Bobrow K, Xia F, Hoang T, Valcour V, Yaffe K (2020) HIV and risk of dementia in older veterans. AIDS 34(11):1673–1679. https://doi.org/10.1097/QAD.0000000000002597
Boehnke SE, Robertson EL, Armitage-Brown B et al (2020) The effect of lumbar puncture on the neurodegeneration biomarker neurofilament light in macaque monkeys. Alzheimers Dement (Amst) 12(1):e12069. https://doi.org/10.1002/dad2.12069
Bradshaw D, Gilleece Y, Verma S, Abramowicz I, Bremner S, Perry N (2020) Protocol for a phase IV, open-label feasibility study investigating non-invasive markers of hepatic fibrosis in people living with HIV-1 and non-alcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT alone. BMJ Open 10(7):e035596. https://doi.org/10.1136/bmjopen-2019-035596
Calcagno A, Atzori C, Romito A et al (2016) Blood brain barrier impairment is associated with cerebrospinal fluid markers of neuronal damage in HIV-positive patients. J Neurovirol 22(1):88–92. https://doi.org/10.1007/s13365-015-0371-x
doi: 10.1007/s13365-015-0371-x pubmed: 26246357
Calcagno A, Barco A, Trunfio M, Bonora S (2018) CNS-Targeted Antiretroviral Strategies: When Are They Needed and What to Choose. Curr HIV/AIDS Rep 15(1):84–91. https://doi.org/10.1007/s11904-018-0375-2
doi: 10.1007/s11904-018-0375-2 pubmed: 29363025
Ciccarelli N, Fabbiani M, Di Giambenedetto S et al (2011) Efavirenz associated with cognitive disorders in otherwise asymptomatic HIV-infected patients. Neurology 76(16):1403–1409. https://doi.org/10.1212/WNL.0b013e31821670fb
doi: 10.1212/WNL.0b013e31821670fb pubmed: 21502598
Ciccarelli N, Fabbiani M, Grima P et al (2014) Liver fibrosis is associated with cognitive impairment in HIV-positive patients. J Int AIDS Soc 17(4 Suppl 3):19722. https://doi.org/10.7448/IAS.17.4.19722
Cysique LA, Casaletto KB, Heaton RK (2021) Reliably Measuring Cognitive Change in the Era of Chronic HIV Infection and Chronic HIV-Associated Neurocognitive Disorders. Curr Top Behav Neurosci 50:271–298. https://doi.org/10.1007/7854_2019_116
doi: 10.1007/7854_2019_116 pubmed: 31559600
De Benedetto I, Trunfio M, Guastamacchia G, Bonora S, Calcagno A (2020) A review of the potential mechanisms of neuronal toxicity associated with antiretroviral drugs. J Neurovirol 26(5):642–651. https://doi.org/10.1007/s13365-020-00874-9
doi: 10.1007/s13365-020-00874-9 pubmed: 32737860
Edén A, Marcotte TD, Heaton RK et al (2016) Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment. Plos One 11(6):e0157160. https://doi.org/10.1371/journal.pone.0157160
doi: 10.1371/journal.pone.0157160 pubmed: 27295036 pmcid: 4905676
Francisci D, Pirro M, Schiaroli E et al (2019) Maraviroc Intensification Modulates Atherosclerotic Progression in HIV-Suppressed Patients at High Cardiovascular Risk. A Randomized, Crossover Pilot Study. Open Forum Infect Dis 6(4):ofz112. https://doi.org/10.1093/ofid/ofz112
Garvey L, Nelson M, Latch N et al (2012) CNS effects of a CCR5 inhibitor in HIV-infected subjects: a pharmacokinetic and cerebral metabolite study. J Antimicrob Chemother 67(1):206–212. https://doi.org/10.1093/jac/dkr427
doi: 10.1093/jac/dkr427 pubmed: 21987241
Gates TM, Cysique LA, Siefried KJ et al (2016) Maraviroc-intensified combined antiretroviral therapy improves cognition in virally suppressed HIV-associated neurocognitive disorder. AIDS 30(4):591–600. https://doi.org/10.1097/QAD.0000000000000951
Gisslén M, Price RW, Andreasson U et al (2015) Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study. EBioMedicine 22(3):135–140. https://doi.org/10.1016/j.ebiom.2015.11.036
doi: 10.1016/j.ebiom.2015.11.036
Gonzalez EO, Boix V, Deltoro MG et al (2014) The effects of Maraviroc on liver fibrosis in HIV/HCV co-infected patients. J Int AIDS Soc 17(4 Suppl 3):19643. https://doi.org/10.7448/IAS.17.4.19643
Guha D, Mukerji SS, Chettimada S et al (2019) Cerebrospinal fluid extracellular vesicles and neurofilament light protein as biomarkers of central nervous system injury in HIV-infected patients on antiretroviral therapy. AIDS 33(4):615–625. https://doi.org/10.1097/QAD.0000000000002121
Haddow LJ, Laverick R, Daskalopoulou M et al (2018) Cognitive impairment in people with hiv in the european region (cipher) study group. Multicenter european prevalence study of neurocognitive impairment and associated factors in hiv positive patients. AIDS Behav 22(5):1573–1583. https://doi.org/10.1007/s10461-017-1683-z
Hammond ER, Crum RM, Treisman GJ et al (2016) CHARTER Group. Persistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study. J Neurovirol 22(4):479–87. https://doi.org/10.1007/s13365-015-0416-1
Han SH, Kim SU, Kim CO et al (2013) Abnormal liver stiffness assessed using transient elastography (Fibroscan®) in HIV-infected patients without HBV/HCV coinfection receiving combined antiretroviral treatment. PLoS ONE 8(1):e52720. https://doi.org/10.1371/journal.pone.0052720
doi: 10.1371/journal.pone.0052720 pubmed: 23300987 pmcid: 3536776
Kelly KM, Beck SE, Metcalf Pate KA et al (2013) Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain. AIDS 27(18):F21–8. https://doi.org/10.1097/QAD.0000000000000074
Lam JO, Hou CE, Hojilla JC et al (2021) Comparison of dementia risk after age 50 between individuals with and without HIV infection. AIDS 35(5):821–828. https://doi.org/10.1097/QAD.0000000000002806
Lemoine M, Assoumou L, De Wit S et al (2019) ANRS-ECHAM Group. Diagnostic accuracy of noninvasive markers of steatosis, nash, and liver fibrosis in hiv-monoinfected individuals at risk of nonalcoholic fatty liver disease (nafld): results from the echam study. J Acquir Immune Defic Syndr 80(4):e86-e94. https://doi.org/10.1097/QAI.0000000000001936
Martin-Blondel G, Brassat D, Bauer J et al (2016) CCR5 blockade for neuroinflammatory diseases–beyond control of HIV. Nat Rev Neurol 12(2):95–105. https://doi.org/10.1038/nrneurol.2015.248
doi: 10.1038/nrneurol.2015.248 pubmed: 26782333
Metral M, Nadin I, Locatelli I et al (2020) Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study group, Swiss HIV Cohort Study. How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population? HIV Med 21(5):342–348. https://doi.org/10.1111/hiv.12828
Mielke MM, Syrjanen JA, Blennow K et al (2019) Plasma and CSF neurofilament light: Relation to longitudinal neuroimaging and cognitive measures. Neurology 93(3):e252–e260. https://doi.org/10.1212/WNL.0000000000007767
Mietelska-Porowska A, Wasik U, Goras M et al (2014) Tau protein modifications and interactions: their role in function and dysfunction. Int J Mol Sci 15(3):4671–713. https://doi.org/10.3390/ijms15034671
Mondi A, Fabbiani M, Ciccarelli N et al (2015) Efficacy and safety of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients with virological suppression: 144 week follow-up of the AtLaS pilot study. J Antimicrob Chemother 70(6):1843–1849. https://doi.org/10.1093/jac/dkv037
doi: 10.1093/jac/dkv037 pubmed: 25885326
Motta I, Allice T, Romito A et al (2017) Cerebrospinal fluid viral load and neopterin in HIV-positive patients with undetectable viraemia. Antivir Ther 22(6):539–543. https://doi.org/10.3851/IMP3140
doi: 10.3851/IMP3140 pubmed: 28198350
Msoka TF, Van Guilder GP, van Furth M et al (2019) The effect of HIV infection, antiretroviral therapy on carotid intima-media thickness: A systematic review and meta-analysis. Life Sci 15(235):116851. https://doi.org/10.1016/j.lfs.2019.116851
doi: 10.1016/j.lfs.2019.116851
Ndhlovu LC, Umaki T, Chew GM et al (2014) Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND). J Neurovirol 20(6):571–582. https://doi.org/10.1007/s13365-014-0279-x
doi: 10.1007/s13365-014-0279-x pubmed: 25227930 pmcid: 4268390
Nightingale S, Winston A, Letendre S et al (2014) Controversies in HIV-associated neurocognitive disorders. Lancet Neurol 13(11):1139–1151. https://doi.org/10.1016/S1474-4422(14)70137-1
doi: 10.1016/S1474-4422(14)70137-1 pubmed: 25316020 pmcid: 4313542
Nweke M, Mshunqane N, Govender N, Akinpelu AO, Ukwuoma M (2022) Impact of HIV-associated cognitive impairment on functional independence, frailty and quality of life in the modern era: a meta-analysis. Sci Rep 12(1):6470. https://doi.org/10.1038/s41598-022-10474-8 . Erratum in: Sci Rep 12(1):10339.
Pérez-Valero I, Pasquau J, Rubio R et al (2018) GESIDA 7011 Study Group members. Neurocognitive safety after 96 weeks on dual therapy with atazanavir/ritonavir plus lamivudine: results of the neurocognitive substudy of the SALT randomized clinical trial. J Antimicrob Chemother 73(9):2444–2451. https://doi.org/10.1093/jac/dky212
Piconi S, Pocaterra D, Rainone V et al (2016) Maraviroc Reduces Arterial Stiffness in PI-Treated HIV-infected Patients. Sci Rep 29(6):28853. https://doi.org/10.1038/srep28853
doi: 10.1038/srep28853
Robertson K, Liner J, Meeker RB (2012) Antiretroviral neurotoxicity. J Neurovirol 18(5):388–399. https://doi.org/10.1007/s13365-012-0120-3
doi: 10.1007/s13365-012-0120-3 pubmed: 22811264 pmcid: 3581315
Sacktor N, Skolasky RL, Moxley R et al (2018) Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment: results from a double-blind, placebo-controlled trial. J Neurovirol 24(1):16–27. https://doi.org/10.1007/s13365-017-0587-z
doi: 10.1007/s13365-017-0587-z pubmed: 29063516
Spencer ME, Jain A, Matteini A et al (2010) Serum levels of the immune activation marker neopterin change with age and gender and are modified by race, BMI, and percentage of body fat. J Gerontol A Biol Sci Med Sci 65(8):858–865. https://doi.org/10.1093/gerona/glq066
doi: 10.1093/gerona/glq066 pubmed: 20478905
Thomas D, Apovian C (2017) Macrophage functions in lean and obese adipose tissue. Metabolism 72:120–143. https://doi.org/10.1016/j.metabol.2017.04.005
doi: 10.1016/j.metabol.2017.04.005 pubmed: 28641779 pmcid: 5516622
Trunfio M, Atzori C, Pasquero M et al (2022) Patterns of cerebrospinal fluid alzheimer's dementia biomarkers in people living with HIV: cross-sectional study on associated factors according to viral control, neurological confounders and neurocognition. Viruses 14(4):753. https://doi.org/10.3390/v14040753
Trunfio M, Rugge W, Mighetto L et al (2020) Dual antiretroviral therapies are effective and safe regimens in the central nervous system of neurologically symptomatic people living with HIV. AIDS 34(13):1899–1906. https://doi.org/10.1097/QAD.0000000000002601
Trunfio M, Vai D, Montrucchio C et al (2018) Diagnostic accuracy of new and old cognitive screening tools for HIV-associated neurocognitive disorders. HIV Med. https://doi.org/10.1111/hiv.12622
doi: 10.1111/hiv.12622 pubmed: 29761877
Underwood J, Robertson KR, Winston A (2015) Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease? AIDS 29(3):253–261. https://doi.org/10.1097/QAD.0000000000000538
doi: 10.1097/QAD.0000000000000538 pubmed: 25426811
Valcour VG, Rubin LH, Obasi MU et al (2016) Womenʼs interagency HIV study protocol team. Liver fibrosis linked to cognitive performance in HIV and hepatitis C. J Acquir Immune Defic Syndr 72(3):266–73. https://doi.org/10.1097/QAI.0000000000000957
Vassallo M, Dunais B, Durant J et al (2013) Relevance of lipopolysaccharide levels in HIV-associated neurocognitive impairment: the Neuradapt study. J Neurovirol 19(4):376–382. https://doi.org/10.1007/s13365-013-0181-y
doi: 10.1007/s13365-013-0181-y pubmed: 23846287
Vassallo M, Fabre R, Durant J et al (2017) A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication. J Neurovirol 23(2):216–225. https://doi.org/10.1007/s13365-016-0490-z
doi: 10.1007/s13365-016-0490-z pubmed: 27815816
Vera JH, Garvey LJ, Allsop JM et al (2012) Alterations in cerebrospinal fluid chemokines are associated with maraviroc exposure and in vivo metabolites measurable by magnetic resonance spectroscopy. HIV Clin Trials 13(4):222–227. https://doi.org/10.1310/hct1304-222
doi: 10.1310/hct1304-222 pubmed: 22849963
Yilmaz A, Verhofstede C, D'Avolio A et al (2010) Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy. J Acquir Immune Defic Syndr 55(5):590–6. https://doi.org/10.1097/QAI.0b013e3181f5b3d1
Yu X, Kuo YF, Raji MA et al (2023) Dementias Among Older Males and Females in the U.S. Medicare System With and Without HIV. J Acquir Immune Defic Syndr 93(2):107–115. https://doi.org/10.1097/QAI.0000000000003184

Auteurs

Giacomo Stroffolini (G)

Department of Medical Sciences, Infectious Diseases Unit, University of Turin, Turin, Italy.
Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.

Alessandro Lazzaro (A)

Department of Medical Sciences, Infectious Diseases Unit, University of Turin, Turin, Italy.
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Ambra Barco (A)

Department of Medical Sciences, Infectious Diseases Unit, University of Turin, Turin, Italy.
Department of Infectious Diseases, Novara Hospital, Novara, Italy.

Veronica Pirriatore (V)

Department of Medical Sciences, Infectious Diseases Unit, University of Turin, Turin, Italy.

Daniela Vai (D)

Maria Vittoria Hospital, Unit of Neurology, Asl Città di Torino, Turin, Italy.

Claudia Giaccone (C)

Maria Vittoria Hospital, Unit of Neurology, Asl Città di Torino, Turin, Italy.

Marco Nigra (M)

San Giovanni Bosco Hospital, Laboratory, Asl Città di Torino, Turin, Italy.

Cristiana Atzori (C)

Maria Vittoria Hospital, Laboratory, Asl Città di Torino, Turin, Italy.

Mattia Trunfio (M)

Department of Medical Sciences, Infectious Diseases Unit, University of Turin, Turin, Italy.

Stefano Bonora (S)

Department of Medical Sciences, Infectious Diseases Unit, University of Turin, Turin, Italy.

Giovanni Di Perri G (G)

Department of Medical Sciences, Infectious Diseases Unit, University of Turin, Turin, Italy.

Andrea Calcagno (A)

Department of Medical Sciences, Infectious Diseases Unit, University of Turin, Turin, Italy. andrea.calcagno@unito.it.

Classifications MeSH