Longitudinal analysis of CSF HIV RNA in untreated people with HIV: Identification of CSF controllers.
CSF control
CSF/plasma discordance
HIV viral load
antiretroviral naïve
blood–brain barrier
central nervous system
Journal
Journal of medical virology
ISSN: 1096-9071
Titre abrégé: J Med Virol
Pays: United States
ID NLM: 7705876
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
revised:
05
03
2024
received:
15
12
2023
accepted:
10
03
2024
medline:
21
3
2024
pubmed:
21
3
2024
entrez:
21
3
2024
Statut:
ppublish
Résumé
Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA < LLQ while plasma HIV RNA > LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p < 0.0001). CSFC (persistent in 7.7% over 3 years) and CSF/plasma discordance (persistent in <0.01% over 1 year) were variably associated with the same parameters (model p < 0.001). Sensitivity analyses confirmed most of the previous associations in participants never exposed to ART. Persistent CSFC was associated with higher CD4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29550Subventions
Organisme : NIMH NIH HHS
ID : P30 MH62512
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH07345
Pays : United States
Organisme : NIMH NIH HHS
ID : R25 MH081482
Pays : United States
Organisme : NIDA NIH HHS
ID : P50 DA26306
Pays : United States
Informations de copyright
© 2024 Wiley Periodicals LLC.
Références
Iuliano R, Forastieri G, Brizzi M, Mecocci L, Mazzotta F, Ceccherini‐Nelli L. Correlation between plasma HIV‐1 RNA levels and the rate of immunologic decline. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14:408‐414.
Probasco JC, Deeks SG, Lee E, et al. Cerebrospinal fluid in HIV‐1 systemic viral controllers: absence of HIV‐1 RNA and intrathecal inflammation. AIDS. 2010;24:1001‐1005.
Hartana CA, Yu XG. Immunological effector mechanisms in HIV‐1 elite controllers. Curr Opin HIV AIDS. 2021;16:243‐248.
Desplats P, Dumaop W, Smith D, et al. Molecular and pathologic insights from latent HIV‐1 infection in the human brain. Neurology. 2013;80:1415‐1423.
Ulfhammer G, Edén A, Antinori A, et al. Cerebrospinal fluid viral load across the spectrum of untreated human immunodeficiency virus type 1 (HIV‐1) infection: a cross‐sectional multicenter study. Clin Infect Dis. 2022;75:493‐502.
Liu Q, Tao W, Yang H, Wu Y, Yu Q, Liu M. Association of high ratio of CSF/plasma HIV‐1 RNA with central nervous system co‐infection in HIV‐1‐positive treatment‐naive patients. Brain Sci. 2022;12:791.
de Almeida SM, Rotta I, de Pereira AP, et al. Cerebrospinal fluid pleocytosis as a predictive factor for CSF and plasma HIV RNA discordance and escape. J Neurovirol. 2020;26:241‐251.
Ellis RJ, Gamst AC, Capparelli E, et al. Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology. 2000;54:927‐936.
Conrad AJ, Schmid P, Syndulko K, et al. Quantifying HIV‐1 RNA using the polymerase chain reaction on cerebrospinal fluid and serum of seropositive individuals with and without neurologic abnormalities. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10:425‐435.
Ellis RJ, Hsia K, Spector SA, et al. Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. Ann Neurol. 1997;42:679‐688.
Brew BJ, Pemberton L, Cunningham P, Law MG. Levels of human immunodeficiency virus type 1 RNA in cerebrospinal fluid correlate with AIDS dementia stage. J Infect Dis. 1997;175:963‐966.
Joseph SB, Gianella S, Burdo TH, et al. Biotypes of central nervous system complications in people with human immunodeficiency virus: virology, immunology, and neuropathology. J Infect Dis. 2023;227:S3‐S15.
Johnson TP, Nath A. Biotypes of HIV‐associated neurocognitive disorders based on viral and immune pathogenesis. Curr Opin Infect Dis. 2022;35:223‐230.
Chaillon A, Gianella S, Dellicour S, et al. HIV persists throughout deep tissues with repopulation from multiple anatomical sources. J Clin Invest. 2020;130:1699‐1712.
Heaton RK, Grant I, Butters N, et al. The HNRC 500‐neuropsychology of HIV infection at different disease stages. J Int Neuropsychol Soc. 1995;1:231‐251.
Heaton RK, Clifford DB, Franklin DR, et al. HIV‐associated neurocognitive disorders persist in the era of potent antiretroviral therapy. Neurology. 2010;75:2087‐2096.
Morgello S, Gelman BB, Kozlowski PB, et al. The National NeuroAIDS Tissue Consortium: a new paradigm in brain banking with an emphasis on infectious disease. Neuropathol Appl Neurobiol. 2001;27:326‐335.
Rippeth JD, Heaton RK, Carey CL, et al. Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons. J Int Neuropsychol Soc. 2004;10:1‐14.
Okwuegbuna OK, Kaur H, Jennifer I, et al. Anemia and erythrocyte indices are associated with neurocognitive performance across multiple ability domains in adults with HIV. J Acquir Immune Defic Syndr. 2023;92:414‐421.
Rand D, Ravid O, Atrakchi D, et al. Endothelial iron homeostasis regulates blood–brain barrier integrity via the HIF2α‐Ve‐cadherin pathway. Pharmaceutics. 2021;13:311.
Fennema‐Notestine C, Thornton‐Wells TA, Hulgan T, et al. Iron‐regulatory genes are associated with neuroimaging measures in HIV infection. Brain Imaging Behav. 2020;14:2037‐2049.
Kallianpur AR, Wang Q, Jia P, et al. Anemia and red blood cell indices predict HIV‐associated neurocognitive impairment in the highly active antiretroviral therapy era. J Infect Dis. 2016;213:1065‐1073.
Russo R, Cristiano C, Avagliano C, et al. Gut‐brain axis: role of lipids in the regulation of inflammation, pain and CNS diseases. Curr Med Chem. 2018;25:3930‐3952.
Rhea EM, Banks WA. Interactions of lipids, lipoproteins, and apolipoproteins with the blood‐brain barrier. Pharm Res. 2021;38:1469‐1475.
Chew H, Solomon VA, Fonteh AN. Involvement of lipids in Alzheimer's disease pathology and potential therapies. Front Physiol. 2020;11:598. https://www.frontiersin.org/articles/10.3389/fphys.2020.00598
Lee LL, Aung HH, Wilson DW, Anderson SE, Rutledge JC, Rutkowsky JM. Triglyceride‐rich lipoprotein lipolysis products increase blood‐brain barrier transfer coefficient and induce astrocyte lipid droplets and cell stress. Am J Physiol Cell Physiol. 2017;312:C500‐C516.
Jones LD, Jackson JW, Maggirwar SB. Modeling HIV‐1 induced neuroinflammation in mice: role of platelets in mediating blood‐brain barrier dysfunction. PLoS One. 2016;11:e0151702.
Singh MV, Davidson DC, Jackson JW, et al. Characterization of platelet‐monocyte complexes in HIV‐1‐infected individuals: possible role in HIV‐associated neuroinflammation. J Immunol. 2014;192:4674‐4684.
Ragin AB, D'Souza G, Reynolds S, et al. Platelet decline as a predictor of brain injury in HIV infection. J Neurovirol. 2011;17:487‐495.
Pretorius E. Platelets in HIV: a guardian of host defence or transient reservoir of the virus? Front Immunol. 2021;12:649465.
Fitzgerald AP, DeGruttola VG, Vaida F. Modelling HIV viral rebound using non‐linear mixed effects models. Stat Med. 2002;21:2093‐2108.
Marcoulides KM, Raykov T. Evaluation of variance inflation factors in regression models using latent variable modeling methods. Educ Psychol Meas. 2019;79:874‐882.
Joseph SB, Arrildt KT, Sturdevant CB, Swanstrom R. HIV‐1 target cells in the CNS. J Neurovirol. 2015;21:276‐289.
Sturdevant CB, Joseph SB, Schnell G, Price RW, Swanstrom R, Spudich S. Compartmentalized replication of R5 T cell‐tropic HIV‐1 in the central nervous system early in the course of infection. PLoS Pathog. 2015;11:e1004720.
Joseph SB, Trunfio M, Kincer LP, Calcagno A, Price RW. What can characterization of cerebrospinal fluid escape populations teach us about viral reservoirs in the central nervous system? AIDS. 2019;33(suppl 2):S171‐S179.
Joseph J, Cinque P, Colosi D, et al. Highlights of the global HIV‐1 CSF escape consortium meeting, 9 June 2016, Bethesda, MD, USA. J Virus Erad. 2016;2:243‐250.
Trunfio M, Pinnetti C, Focà E, et al. Cerebrospinal fluid HIV‐1 escape according to different thresholds and underlying comorbidities: is it time to assess the definitions? AIDS. 2019;33:759‐762.
Mukerji SS, Misra V, Lorenz DR, et al. Impact of antiretroviral regimens on cerebrospinal fluid viral escape in a prospective multicohort study of antiretroviral therapy‐experienced human immunodeficiency virus‐1‐infected adults in the United States. Clin Infect Dis. 2018;67:1182‐1190.
Trunfio M, Pinnetti C, Arsuffi S, et al. The presence of resistance‐associated mutations in reverse transcriptase gene is associated with cerebrospinal fluid HIV‐1 escape: a multicentric retrospective analysis. J Med Virol 2023;
Calcagno A, Barco A, Trunfio M, Bonora S. CNS‐targeted antiretroviral strategies: when are they needed and what to choose. Curr HIV/AIDS Rep. 2018;15:84‐91.
Hightower GK, Letendre SL, Cherner M, et al. Select resistance‐associated mutations in blood are associated with lower CSF viral loads and better neuropsychological performance. Virology. 2009;394:243‐248.
Giridhar K, Ritica S, Deepti C, Shet AS. Serum hepcidin detects iron deficiency anemia in HIV infected patients with anemia of inflammation. Blood. 2015;126:944.
Di Marco LY, Venneri A, Farkas E, Evans PC, Marzo A, Frangi AF. Vascular dysfunction in the pathogenesis of Alzheimer's disease—a review of endothelium‐mediated mechanisms and ensuing vicious circles. Neurobiol Dis. 2015;82:593‐606.
Gros A, Ollivier V, Ho‐Tin‐Noé B. Platelets in inflammation: regulation of leukocyte activities and vascular repair. Front Immunol. 2015;5:678. https://www.frontiersin.org/articles/10.3389/fimmu.2014.00678
Kim AH, Jang W, Kim Y, Park YJ, Han K, Oh EJ. Mean corpuscular volume (MCV) values reflect therapeutic effectiveness in Zidovudine‐receiving HIV patients. J Clin Lab Anal. 2013;27:373‐378.