Plasma biomarker factors associated with neurodevelopmental outcomes in children with perinatal HIV infection and controlled viremia.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
15 07 2021
15 07 2021
Historique:
pubmed:
13
3
2021
medline:
7
8
2021
entrez:
12
3
2021
Statut:
ppublish
Résumé
We examined relationships between plasma biomarkers and neurodevelopment in children from sub-Saharan Africa with perinatal HIV (PHIV) with controlled viremia on antiretroviral therapy (ART). Longitudinal retrospective cohort study of children with controlled blood HIV replication. Children (N = 213; 57% girls) started ART at less than 3 years of age, had neurodevelopmental assessments (cognition, attention/impulsivity, motor proficiency, global executive functions) at 5-11 years, and achieved controlled viremia (HIV-1 RNA <400 copies/ml for ≥9 months before initial assessment). Twenty-three plasma biomarkers were measured at onset of controlled viremia, week 0 (first neurodevelopmental assessment), and week 48 (second neurodevelopmental assessment). Factor analysis was conducted at each time point. Multivariable linear regressions assessed associations between factors and neurodevelopmental scores. Median age at week 0 was 7.0 years. Eighteen biomarkers loaded on six factors: a (L-10, IFNγ, IFNα2, IL-1β, IL-6, IP-10, TNFα); B (sCD163, sICAM-1, sVCAM-1, CRP); C (sE-selectin, sP-selectin); D [MIP-1β, vascular endothelial growth factor (VEGF)-A]; E (sCD14, CRP); and F (CX3CL1, MCP-1). Higher factor B scores were consistently associated with worse cognition and attention/impulsivity, and higher factor D scores with better attention/impulsivity. These results suggest a detrimental effect of increased endothelial cell activation (sICAM-1, sVCAM-1) and monocyte/macrophage scavenger function (sCD163) and a beneficial effect of increased CCR5 ligand and HIV entry blocker MIP-1β and angiogenesis stimulant-VEGF concentrations on the neurodevelopment of children with PHIV. The model that emerges is of vascular inflammation leading to neurodevelopmental deficits. The role of persistent HIV replication in the central nervous system also needs to be further explored.
Identifiants
pubmed: 33710019
doi: 10.1097/QAD.0000000000002862
pii: 00002030-202107150-00005
pmc: PMC8243791
mid: NIHMS1679713
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1375-1384Subventions
Organisme : NICHD NIH HHS
ID : HHSN275201800001C
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068632
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068616
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106716
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275201800001I
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Boivin MJ, Chernoff M, Fairlie L, Laughton B, Zimmer B, Joyce C, et al. African multi-site 2-year neuropsychological study of school-age children perinatally infected, exposed, and unexposed to human immunodeficiency virus . Clin Infect Dis 2020; 71:e105–e114.
Benki-Nugent SF, Martopullo I, Laboso T, Tamasha N, Wamalwa DC, Tapia K, et al. High plasma soluble CD163 during infancy is a marker for neurocognitive outcomes in early-treated HIV-infected children . J Acquir Immune Defic Syndr 2019; 81:102–109.
Ananworanich J, Kerr SJ, Jaimulwong T, Vibol U, Hansudewechakul R, Kosalaraksa P, et al. Soluble CD163 and monocyte populations in response to antiretroviral therapy and in relationship with neuropsychological testing among HIV-infected children . J Virus Erad 2015; 1:196–202.
Kapetanovic S, Leister E, Nichols S, Miller T, Tassiopoulos K, Hazra R, et al. Pediatric HIV/AIDS Cohort Study Team. Relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected youth . AIDS 2010; 24:1481–1491.
Kapetanovic S, Griner R, Zeldow B, Nichols S, Leister E, Gelbard HA, et al. Pediatric HIV/AIDS Cohort Study Team. Biomarkers and neurodevelopment in perinatally HIV-infected or exposed youth: a structural equation model analysis . AIDS 2014; 28:355–364.
Neaton JD, Neuhaus J, Emery S. Soluble biomarkers and morbidity and mortality among people infected with HIV: summary of published reports from 1997 to 2010 . Curr Opin HIV AIDS 2010; 5:480–490.
Leeansyah E, Malone DF, Anthony DD, Sandberg JK. Soluble biomarkers of HIV transmission, disease progression and comorbidities . Curr Opin HIV AIDS 2013; 8:117–124.
Violari A, Lindsey JC, Hughes MD, Mujuru HA, Barlow-Mosha L, Kamthunzi P, et al. Nevirapine versus ritonavir-boosted lopinavir for HIV-infected children . N Engl J Med 2012; 366:2380–2389.
Boivin MJ, Barlow-Mosha L, Chernoff MC, Laughton B, Zimmer B, Joyce C, et al. IMPAACT P1104s Study Team. Neuropsychological performance in African children with HIV enrolled in a multisite antiretroviral clinical trial . AIDS 2018; 32:189–204.
Chernoff MC, Laughton B, Ratswana M, Familiar I, Fairlie L, Vhembo T, et al. Validity of neuropsychological testing in young African children affected by HIV . J Pediatr Infect Dis 2018; 13:185–201.
Boivin MJ, Ruel TD, Boal HE, Bangirana P, Cao H, Eller LA, et al. HIV-subtype A is associated with poorer neuropsychological performance compared with subtype D in antiretroviral therapy-naive Ugandan children . AIDS 2010; 24:1163–1170.
Ruel TD, Boivin MJ, Boal HE, Bangirana P, Charlebois E, Havlir DV, et al. Neurocognitive and motor deficits in HIV-infected Ugandan children with high CD4 cell counts . Clin Infect Dis 2012; 54:1001–1009.
O’Rourke N, Hatcher L. A step-by-step approach to using SAS for factor analysis and structural equation modeling . 2nd edCary, North Carolina: SAS Institute Inc; 2013.
Rothman KJ. No adjustments are needed for multiple comparisons . Epidemiology 1990; 1:43–46.
Blume J, Peipert JF. What your statistician never told you about P-values . J Am Assoc Gynecol Laparosc 2003; 10:439–444.
Althouse AD. Adjust for multiple comparisons? It's not that simple . Ann Thorac Surg 2016; 101:1644–1645.
Nagel T, Resnick N, Atkinson WJ, Dewey CF Jr, Gimbrone MA Jr. Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells . J Clin Invest 1994; 94:885–891.
Bruyndoncky L, Hoymans VY, Van Craenenbroeck AH, Vissers DK, Vrints CJ, Ramet J, Conraads VM, et al. Assessment of endothelial dysfunction in childhood obesity and clinical use . Oxid Med Cell Longev 2013; 2013:174782.
Burdo TH, Lentz MR, Autissier P, Krishnan A, Halpern E, Letendre S, et al. Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after antiretroviral therapy . J Infect Dis 2011; 204:154–163.
D’Antoni ML, Byron MM, Chan P, Sailasuta N, Sacdalan C, Sithinamsuwan P, et al. RV254/SEARCH010, SEARCH011, and RV304/SEARCH013 Study Groups. Normalization of soluble CD163 levels after institution of antiretroviral therapy during acute HIV infection tracks with fewer neurological abnormalities . J Infect Dis 2018; 218:1453–1463.
Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O'Shea KS, et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene . Nature 1996; 380:439–442.
Jin KL, Mao XO, Greenberg DA. Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia . Proc Natl Acad Sci USA 2000; 97:10242–10247.
Storkebaum E, Lambrechts D, Dewerchin M, Moreno-Murciano MP, Appelmans S, Oh H, et al. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS . Nat Neurosci 2005; 8:85–92.
Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele . Nature 1996; 380:435–439.
Obuku AE, Bugembe DL, Musinguzi K, Serwanga J, Ndembi N, Levin J, et al. Macrophage inflammatory protein-1 beta and interferon gamma responses in Ugandans with HIV-1 acute/early infections . AIDS Res Hum Retroviruses 2016; 32:237–246.
D'Antoni ML, Paul RH, Mitchell BI, Kohorn L, Fischer L, Lefebvre E, et al. Improved cognitive performance and reduced monocyte activation in virally suppressed chronic HIV after dual CCR2 and CCR5 antagonism . J Acquir Immune Defic Syndr 2018; 79:108–116.
Li G, Kim YJ, Mantel C, Broxmeyer HE. P-selectin enhances generation of CD14+CD16+ dendritic-like cells and inhibits macrophage maturation from human peripheral blood monocytes . J Immunol 2003; 171:669–677.
Klatt NR, Funderburg NT, Brenchley JM. Microbial translocation, immune activation, and HIV disease . Trends Microbiol 2013; 21:6–13.
Younas M, Psomas C, Reynes C, Cezar R, Kundura L, Portales P, et al. Microbial translocation is linked to a specific immune activation profile in HIV-1-Infected adults with suppressed viremia . Front Immunol 2019; 10:2185.
De Voeght A, Maes N, Moutschen M. sCD14 is not a bona-fide biomarker of microbial translocation in HIV-1-infected Africans living in Belgium . AIDS 2016; 30:921–924.
Familiar I, Chernoff M, Ruisenor-Escudero H, Laughton B, Joyce C, Fairlie L, et al. Association between caregiver depression symptoms and child executive functioning. Results from an observational study carried out in four sub-Saharan countries . AIDS Care 2020; 32:486–494.