220
Views
0
CrossRef citations to date
0
Altmetric
Review

Neurodevelopmental delay in pediatric HIV/AIDS: current perspectives

, , &
Pages 1-13 | Published online: 13 Jan 2016

References

  • World Health Organization. Global Update on the Health Sector Response to HIV, 2014. Geneva: WHO; 2014.
  • Valcour V, Chalermchai T, Sailasuta N, et al. Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis. 2012;206(2):275–282.
  • Patel K, Ming X, Williams PL, Robertson KR, Oleske JM, Seage GR. Impact of HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents. AIDS. 2009;23(14):1893–1901.
  • Tardieu M, Le Chenadec J, Persoz A, Meyer L, Blanche S, Mayaux MJ. HIV-1-related encephalopathy in infants compared with children and adults. French Pediatric HIV Infection Study and the SEROCO Group. Neurology. 2000;54(5):1089–1095.
  • Cohen S, Ter Stege JA, Geurtsen GJ, et al. Poorer cognitive performance in perinatally HIV-infected children versus healthy socioeconomically matched controls. Clin Infect Dis. 2015;60(7):1111–1119.
  • Tau GZ, Peterson BS. Normal development of brain circuits. Neuropsychopharmacology. 2010;35(1):147–168.
  • Spudich S, González-Scarano F. HIV-1-related central nervous system disease: current issues in pathogenesis, diagnosis, and treatment. Cold Spring Harb Perspect Med. 2012;2(6):a007120.
  • Van Rie A, Harrington PR, Dow A, Robertson K. Neurologic and neurodevelopmental manifestations of pediatric HIV/AIDS: a global perspective. Eur J Paediatr Neurol. 2007;11(1):1–9.
  • Puthanakit T, Ananworanich J, Vonthanak S, et al. Cognitive function and neurodevelopmental outcomes in HIV-infected children older than 1 year of age randomized to early versus deferred antiretroviral therapy: the PREDICT neurodevelopmental study. Pediatr Infect Dis J. 2013;32(5):501–508.
  • Le Doaré K, Bland R, Newell ML. Neurodevelopment in children born to HIV-infected mothers by infection and treatment status. Pediatrics. 2012;130(5):e1326–e1344.
  • Lindsey JC, Malee KM, Brouwers P, Hughes MD. Neurodevelopmental functioning in HIV-infected infants and young children before and after the introduction of protease inhibitor-based highly active antiretroviral therapy. Pediatrics. 2007;119(3):e681–e693.
  • Ferguson G, Jelsma J. The prevalence of motor delay among HIV infected children living in Cape Town, South Africa. Int J Rehabil Res. 2009;32(2):108–114.
  • Laughton B, Cornell M, Grove D, et al. Early antiretroviral therapy improves neurodevelopmental outcomes in infants. AIDS. 2012;26(13):1685–1690.
  • Chase C, Ware J, Hittelman J, et al. Early cognitive and motor development among infants born to women infected with human immunodeficiency virus. Women and Infants Transmission Study Group. Pediatrics. 2000;106(2):E25.
  • Jeremy RJ, Kim S, Nozyce M, et al. Neuropsychological functioning and viral load in stable antiretroviral therapy-experienced HIV-infected children. Pediatrics. 2005;115(2):380–387.
  • Ruel TD, Boivin MJ, Boal HE, et al. Neurocognitive and motor deficits in HIV-infected Ugandan children with high CD4 cell counts. Clin Infect Dis. 2012;54(7):1001–1009.
  • Lowick S, Sawry S, Meyers T. Neurodevelopmental delay among HIV-infected preschool children receiving antiretroviral therapy and healthy preschool children in Soweto, South Africa. Psychol Health Med. 2012;17(5):599–610.
  • Kandawasvika GQ, Kuona P, Chandiwana P, et al. The burden and predictors of cognitive impairment among 6- to 8-year-old children infected and uninfected with HIV from Harare, Zimbabwe: a cross-sectional study. Child Neuropsychol. 2015;21(1):106–120.
  • Fishkin PE. Brief report: Relationship between HIV infection and WPPSI-R performance in preschool-age children. J Pediatr Psychol. 2000;25(5):347–351.
  • Koekkoek S, de Sonneville LM, Wolfs TF, Licht R, Geelen SP. Neurocognitive function profile in HIV-infected school-age children. Eur J Paediatr Neurol. 2008;12(4):290–297.
  • Laughton B, Cornell M, Boivin M, Van Rie A. Neurodevelopment in perinatally HIV-infected children: a concern for adolescence. J Int AIDS Soc. 2013;16(1):18603.
  • Whitehead N, Potterton J, Coovadia A. The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but uninfected infants. AIDS Care. 2014;26(4):497–504.
  • Brahmbhatt H, Boivin M, Ssempijja V, et al. Neurodevelopmental benefits of antiretroviral therapy in Ugandan children aged 0–6 years with HIV. J Acquir Immune Defic Syndr. 2014;67(3):316–322.
  • Brackis-Cott E, Kang E, Dolezal C, Abrams EJ, Mellins CA. The impact of perinatal HIV infection on older school-aged children’s and adolescents’ receptive language and word recognition skills. AIDS Patient Care STDS. 2009;23(6):415–421.
  • Van Rie A, Mupuala A, Dow A. Impact of the HIV/AIDS epidemic on the neurodevelopment of preschool-aged children in Kinshasa, Democratic Republic of the Congo. Pediatrics. 2008;122(1):e123–e128.
  • Rice ML, Buchanan AL, Siberry GK, et al. Language impairment in children perinatally infected with HIV compared to children who were HIV-exposed and uninfected. J Dev Behav Pediatr. 2012;33(2):112–123.
  • Souza E, Santos N, Valentini S, Silva G, Falbo A. Long-term follow-up outcomes of perinatally HIV-infected adolescents: infection control but school failure. J Trop Pediatr. 2010;56(6):421–426.
  • Wood SM, Shah SS, Steenhoff AP, Rutstein RM. The impact of AIDS diagnoses on long-term neurocognitive and psychiatric outcomes of surviving adolescents with perinatally acquired HIV. AIDS. 2009;23(14):1859–1865.
  • Kerr SJ, Puthanakit T, Vibol U, et al. Neurodevelopmental outcomes in HIV-exposed-uninfected children versus those not exposed to HIV. AIDS Care. 2014;26(11):1–9.
  • Lyman WD, Kress Y, Kure K, Rashbaum WK, Rubinstein A, Soeiro R. Detection of HIV in fetal central nervous system tissue. AIDS. 1990;4(9):917–920.
  • Williams PL, Marino M, Malee K, Brogly S, Hughes MD, Mofenson LM. Neurodevelopment and in utero antiretroviral exposure of HIV-exposed uninfected infants. Pediatrics. 2010;125(2):e250–e260.
  • Crowell CS, Malee KM, Yogev R, Muller WJ. Neurologic disease in HIV-infected children and the impact of combination antiretroviral therapy. Rev Med Virol. 2014;24(5):316–331.
  • Chiriboga CA, Fleishman S, Champion S, Gaye-Robinson L, Abrams EJ. Incidence and prevalence of HIV encephalopathy in children with HIV infection receiving highly active anti-retroviral therapy (HAART). J Pediatr. 2005;146(3):402–407.
  • Smith R, Chernoff M, Williams PL, et al. Impact of HIV severity on cognitive and adaptive functioning during childhood and adolescence. Pediatr Infect Dis J. 2012;31(6):592–598.
  • Nachman S, Chernoff M, Williams P, Hodge J, Heston J, Gadow KD. Human immunodeficiency virus disease severity, psychiatric symptoms, and functional outcomes in perinatally infected youth. Arch Pediatr Adolesc Med. 2012;166(6):528–535.
  • Kandawasvika GQ, Ogundipe E, Gumbo FZ, Kurewa EN, Mapingure MP, Stray-Pedersen B. Neurodevelopmental impairment among infants born to mothers infected with human immunodeficiency virus and uninfected mothers from three peri-urban primary care clinics in Harare, Zimbabwe. Dev Med Child Neurol. 2011;53(11):1046–1052.
  • Smith R, Malee K, Charurat M, et al. Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment. Pediatr Infect Dis J. 2000;19(9):862–871.
  • Hoare J, Fouche JP, Spottiswoode B, et al. A diffusion tensor imaging and neurocognitive study of HIV-positive children who are HAART-naïve “slow progressors”. J Neurovirol. 2012;18(3):205–212.
  • McCoig C, Castrejón MM, Castaño E, et al. Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy. J Pediatr. 2002;141(1):36–44.
  • Nightingale S, Winston A, Letendre S, et al. Controversies in HIV-associated neurocognitive disorders. Lancet Neurol. 2014;13(11):1139–1151.
  • Chan P, Brew BJ. HIV associated neurocognitive disorders in the modern antiviral treatment era: prevalence, characteristics, biomarkers, and effects of treatment. Curr HIV/AIDS Rep. 2014;11(3):317–324.
  • Edén A, Fuchs D, Hagberg L, et al. HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis. 2010;202(12):1819–1825.
  • Canestri A, Lescure FX, Jaureguiberry S, et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis. 2010;50(5):773–778.
  • Ross AC, O’Riordan MA, Storer N, Dogra V, McComsey GA. Heightened inflammation is linked to carotid intima-media thickness and endothelial activation in HIV-infected children. Atherosclerosis. 2010;211(2):492–498.
  • Kapetanovic S, Leister E, Nichols S, et al. Relationships between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected youth. AIDS. 2010;24(10):1481–1491.
  • Kamat A, Lyons J, Misra V. Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection. J Acquir Immune Defic Syndr. 2012;60(3):234–243.
  • Robertson K, Liner J, Meeker RB. Antiretroviral neurotoxicity. J Neurovirol. 2012;18(5):388–399.
  • Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011;12(12):723–738.
  • Hong S, Banks WA. Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications. Brain Behav Immun. 2015;45:1–12.
  • Chaudhuri A, Duan F, Morsey B, Persidsky Y, Kanmogne GD. HIV-1 activates proinflammatory and interferon-inducible genes in human brain microvascular endothelial cells: putative mechanisms of blood-brain barrier dysfunction. J Cereb Blood Flow Metab. 2008;28(4):697–711.
  • Stins MF, Shen Y, Huang SH, Gilles F, Kalra VK, Kim KS. Gp120 activates children’s brain endothelial cells via CD4. J Neurovirol. 2001;7(2):125–134.
  • Muratori C, Mangino G, Affabris E, Federico M. Astrocytes contacting HIV-1-infected macrophages increase the release of CCL2 in response to the HIV-1-dependent enhancement of membrane-associated TNFα in macrophages. Glia. 2010;58(16):1893–1904.
  • Dohgu S, Banks WA. Brain pericytes increase the lipopolysaccharide-enhanced transcytosis of HIV-1 free virus across the in vitro blood-brain barrier: evidence for cytokine-mediated pericyte-endothelial cell crosstalk. Fluids Barriers CNS. 2013;10(1):23.
  • Louboutin JP, Agrawal L, Reyes BA, Van Bockstaele EJ, Strayer DS. HIV-1 gp120-induced injury to the blood-brain barrier: role of metalloproteinases 2 and 9 and relationship to oxidative stress. J Neuropathol Exp Neurol. 2010;69(8):801–816.
  • Rao VR, Ruiz AP, Prasad VR. Viral and cellular factors underlying neuropathogenesis in HIV associated neurocognitive disorders (HAND). AIDS Res Ther. 2014;11(1):13.
  • Trillo-Pazos G, Diamanturos A, Rislove L, et al. Detection of HIV-1 DNA in microglia/macrophages, astrocytes and neurons isolated from brain tissue with HIV-1 encephalitis by laser capture microdissection. Brain Pathol. 2003;13(1):144–154.
  • Sabri F, Tresoldi E, Di Stefano M, et al. Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors. Virology. 1999;264(2):370–384.
  • Kramer-Hämmerle S, Rothenaigner I, Wolff H, Bell JE, Brack-Werner R. Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res. 2005;111(2):194–213.
  • Schwartz L, Major EO. Neural progenitors and HIV-1-associated central nervous system disease in adults and children. Curr HIV Res. 2006;4(3):319–327.
  • Krathwohl MD, Kaiser JL. HIV-1 promotes quiescence in human neural progenitor cells. J Infect Dis. 2004;190(2):216–226.
  • An SF, Groves M, Gray F, Scaravilli F. Early entry and widespread cellular involvement of HIV-1 DNA in brains of HIV-1 positive asymptomatic individuals. J Neuropathol Exp Neurol. 1999;58(11):1156–1162.
  • Meucci O, Fatatis A, Simen AA, Bushell TJ, Gray PW, Miller RJ. Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci U S A. 1998;95(24):14500–14505.
  • Bachis A, Biggio F, Major EO, Mocchetti I. M- and T-tropic HIVs promote apoptosis in rat neurons. J Neuroimmune Pharmacol. 2009;4(1):150–160.
  • Eugenin EA, King JE, Nath A, et al. HIV-tat induces formation of an LRP-PSD-95-NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc Natl Acad Sci U S A. 2007;104(9):3438–3443.
  • Jones GJ, Barsby NL, Cohen EA, et al. HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration. J Neurosci. 2007;27(14):3703–3711.
  • Huang Y, Zhao L, Jia B, et al. Glutaminase dysregulation in HIV-1-infected human microglia mediates neurotoxicity: relevant to HIV-1-associated neurocognitive disorders. J Neurosci. 2011;31(42):15195–15204.
  • Wang Z, Pekarskaya O, Bencheikh M, et al. Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120. Virology. 2003;312(1):60–73.
  • Self RL, Mulholland PJ, Nath A, Harris BR, Prendergast MA. The human immunodeficiency virus type-1 transcription factor Tat produces elevations in intracellular Ca2+ that require function of an N-methyl-d-aspartate receptor polyamine-sensitive site. Brain Res. 2004;995(1):39–45.
  • Gemignani A, Paudice P, Pittaluga A, Raiteri M. The HIV-1 coat protein gp120 and some of its fragments potently activate native cerebral NMDA receptors mediating neuropeptide release. Eur J Neurosci. 2000;12(8):2839–2846.
  • Melli G, Keswani SC, Fischer A, Chen W, Höke A. Spatially distinct and functionally independent mechanisms of axonal degeneration in a model of HIV-associated sensory neuropathy. Brain. 2006;129(Pt 5):1330–1338.
  • Liu X, Jana M, Dasgupta S, et al. Human immunodeficiency virus type 1 (HIV-1) tat induces nitric-oxide synthase in human astroglia. J Biol Chem. 2002;277(42):39312–39319.
  • Bernardo A, Agresti C, Levi G. HIV-gp120 affects the functional activity of oligodendrocytes and their susceptibility to complement. J Neurosci Res. 1997;50(6):946–957.
  • Hauser KF, Hahn YK, Adjan VV, et al. HIV-1 Tat and morphine have interactive effects on oligodendrocyte survival and morphology. Glia. 2009;57(2):194–206.
  • Peluso MJ, Meyerhoff DJ, Price RW, et al. Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. J Infect Dis. 2013;207(11):1703–1712.
  • Burdo TH, Weiffenbach A, Woods SP, Letendre S, Ellis RJ, Williams KC. Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection. AIDS. 2013;27(9):1387–1395.
  • McGuire J, Gill A, Douglas S, Kolson D. Central and peripheral markers of neurodegeneration and monocyte activation in HIV-associated neurocognitive disorders. J Neurovirol. 2015;21(4):439–448.
  • Fischer-Smith T, Croul S, Sverstiuk AE, et al. CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol. 2001;7(6):528–541.
  • Williams DW, Calderon TM, Lopez L, et al. Mechanisms of HIV entry into the CNS: increased sensitivity of HIV infected CD14+CD16+ monocytes to CCL2 and key roles of CCR2, JAM-A, and ALCAM in diapedesis. PLoS One. 2013;8(7):e69270.
  • Syed SS, Balluz RS, Kabagambe EK, et al. Assessment of biomarkers of cardiovascular risk among HIV-1 infected adolescents: role of soluble vascular cell adhesion molecule (sVCAM) as an early indicator of endothelial inflammation. AIDS Res Hum Retroviruses. 2013;29(3):493–500.
  • Sainz T, Diaz L, Navarro ML, et al. Cardiovascular biomarkers in vertically HIV-infected children without metabolic abnormalities. Atherosclerosis. 2014;233(2):410–414.
  • Anderson AM, Harezlak J, Bharti A, et al. Plasma and cerebrospinal fluid biomarkers predict cerebral injury in HIV-infected individuals on stable combination antiretroviral therapy. J Acquir Immune Defic Syndr. 2015;69(1):29–35.
  • McCoig C, Castrejón MM, Saavedra-Lozano J, et al. Cerebrospinal fluid and plasma concentrations of proinflammatory mediators in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2004;23(2):114–118.
  • Ye L, Huang Y, Zhao L, et al. IL-1β and TNF-α induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase. J Neurochem. 2013;125(6):897–908.
  • Wilt SG, Milward E, Zhou JM, et al. In vitro evidence for a dual role of tumor necrosis factor-α in human immunodeficiency virus type 1 encephalopathy. Ann Neurol. 1995;37(3):381–394.
  • Yang B, Akhter S, Chaudhuri A, Kanmogne GD. HIV-1 gp120 induces cytokine expression, leukocyte adhesion, and transmigration across the blood-brain barrier: modulatory effects of STAT1 signaling. Microvasc Res. 2009;77(2):212–219.
  • González-Scarano F, Martín-García J. The neuropathogenesis of AIDS. Nat Rev Immunol. 2005;5(1):69–81.
  • Kaul M, Lipton SA. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proc Natl Acad Sci U S A. 1999;96(14):8212–8216.
  • Eugenin EA, D’Aversa TG, Lopez L, Calderon TM, Berman JW. MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. J Neurochem. 2003;85(5):1299–1311.
  • Marchetti L, Klein M, Schlett K, Pfizenmaier K, Eisel ULM. Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation: essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-κB pathway. J Biol Chem. 2004;279(31):32869–32881.
  • Hoare J, Ransford GL, Phillips N, Amos T, Donald K, Stein DJ. Systematic review of neuroimaging studies in vertically transmitted HIV positive children and adolescents. Metab Brain Dis. 2014;29(2):221–229.
  • van Arnhem LA, Bunders MJ, Scherpbier HJ, et al. Neurologic abnormalities in HIV-1 infected children in the era of combination antiretroviral therapy. PLoS One. 2013;8(5):e64398.
  • Cohen S, Caan M, Mutsaerts H, et al. Cerebral injury in perinatally HIV-infected children compared to matched healthy controls. Neurology. In press 2015.
  • Martin SC, Wolters PL, Toledo-Tamula MA, Zeichner SL, Hazra R, Civitello L. Cognitive functioning in school-aged children with vertically acquired HIV infection being treated with highly active antiretroviral therapy (HAART). Dev Neuropsychol. 2006;30(2):633–657.
  • Ackermann C, Andronikou S, Laughton B, et al. White matter signal abnormalities in children with suspected HIV-related neurologic disease on early combination antiretroviral therapy. Pediatr Infect Dis J. 2014;33(8):e207–e212.
  • Kure K, Llena JF, Lyman WD, et al. Human immunodeficiency virus-1 infection of the nervous system: an autopsy study of 268 adult, pediatric, and fetal brains. Hum Pathol. 1991;22(7):700–710.
  • Kim KW, MacFall JR, Payne ME. Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biol Psychiatry. 2008;64(4):273–280.
  • Hoare J, Fouche JP, Phillips N, et al. Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa. J Neurovirol. 2015;21(2):120–128.
  • Peterson J, Gisslen M, Zetterberg H, et al. Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection. PLoS One. 2014;9(12):e116081.
  • Calcagno A, Atzori C, Romito A, et al. Cerebrospinal fluid biomarkers in patients with plasma HIV RNA below 20 copies/mL. J Int AIDS Soc. 2014;17(4 Suppl 3):19719.
  • Achim CL, Adame A, Dumaop W, Everall IP, Masliah E. Increased accumulation of intraneuronal amyloid β in HIV-infected patients. J Neuroimmune Pharmacol. 2009;4(2):190–199.
  • Shahim P, Darin N, Andreasson U, et al. Cerebrospinal fluid brain injury biomarkers in children: a multicenter study. Pediatr Neurol. 2013;49(1):31–39. e2.
  • Masters MC, Ances BM. Role of neuroimaging in HIV-associated neurocognitive disorders. Semin Neurol. 2014;34(1):89–102.
  • Young AC, Yiannoutsos CT, Hegde M, et al. Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection. Neurology. 2014;83(18):1592–1600.
  • Gabis L, Belman A, Huang W, Milazzo M, Nachman S. Clinical and imaging study of human immunodeficiency virus-1-infected youth receiving highly active antiretroviral therapy: pilot study using magnetic resonance spectroscopy. J Child Neurol. 2006;21(6):486–490.
  • Prado PT, Escorsi-Rosset S, Cervi MC, Santos AC. Image evaluation of HIV encephalopathy: a multimodal approach using quantitative MR techniques. Neuroradiology. 2011;53(11):899–908.
  • Keller MA, Venkatraman TN, Thomas A, et al. Altered neurometabolite development in HIV-infected children: correlation with neuropsychological tests. Neurology. 2004;62(10):1810–1817.
  • Rae CD. A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res. 2014;39(1):1–36.
  • Mohamed MA, Barker PB, Skolasky RL, et al. Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic resonance spectroscopy study. Magn Reson Imaging. 2010;28(9):1251–1257.
  • Cohen RA, Harezlak J, Gongvatana A, et al. Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. J Neurovirol. 2010;16(6):435–444.
  • Shah SS, Zimmerman RA, Rorke LB, Vezina LG. Cerebrovascular complications of HIV in children. Am J Neuroradiol. 1996;17(10):1913–1917.
  • Wilmshurst JM, Donald KA, Eley B. Update on the key developments of the neurologic complications in children infected with HIV. Curr Opin HIV AIDS. 2014;9(6):533–538.
  • Miller TL, Borkowsky W, Dimeglio LA, et al. Metabolic abnormalities and viral replication are associated with biomarkers of vascular dysfunction in HIV-infected children. HIV Med. 2012;13(5):264–275.
  • Charakida M, Donald AE, Green H, et al. Early structural and functional changes of the vasculature in HIV-infected children: impact of disease and antiretroviral therapy. Circulation. 2005;112(1):103–109.
  • Idris N, Grobbee D, Burgner D, et al. Cardiovascular manifestations of HIV infection in children. Eur J Prev Cardiol. 2015;22(11):1452–1461.
  • Depas G, Chiron C, Tardieu M, et al. Functional brain imaging in HIV-1-infected children born to seropositive mothers. J Nucl Med. 1995;36(12):2169–2174.
  • Tracey I, Hamberg LM, Guimaraes AR, et al. Increased cerebral blood volume in HIV-positive patients detected by functional MRI. Neurology. 1998;50(6):1821–1826.
  • Ances BM, Sisti D, Vaida F, et al. Resting cerebral blood flow: a potential biomarker of the effects of HIV in the brain. Neurology. 2009;73(9):702–708.
  • Ances BM, Roc AC, Wang J, et al. Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired patients. Neurology. 2006;66(6):862–866.
  • Melrose RJ, Tinaz S, Castelo JM, Courtney MG, Stern CE. Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing. Behav Brain Res. 2008;188(2):337–347.
  • Towgood KJ, Pitkanen M, Kulasegaram R, et al. Regional cerebral blood flow and FDG uptake in asymptomatic HIV-1 men. Hum Brain Mapp. 2013;34(10):2484–2493.
  • Kilroy E, Liu CY, Yan L, et al. Relationships between cerebral blood flow and IQ in typically developing children and adolescents. J Cogn Sci (Seoul). 2011;12(2):151–170.
  • Lazarus JR, Rutstein RM, Lowenthal ED. Treatment initiation factors and cognitive outcome in youth with perinatally acquired HIV infection. HIV Med. 2015;16(6):355–361.
  • Crowell CS, Huo Y, Tassiopoulos K, et al. Early viral suppression improves neurocognitive outcomes in HIV-infected children. AIDS. 2015;29(3):295–304.
  • Svicher V, Ceccherini-Silberstein F, Antinori A, Aquaro S, Perno CF. Understanding HIV compartments and reservoirs. Curr HIV/AIDS Rep. 2014;11(2):186–194.
  • Tamula MA, Wolters PL, Walsek C, Zeichner S, Civitello L. Cognitive decline with immunologic and virologic stability in four children with human immunodeficiency virus disease. Pediatrics. 2003;112(3):679–684.
  • Price RW, Spudich S. Antiretroviral therapy and central nervous system HIV type 1 infection. J Infect Dis. 2008;197(Suppl 3):S294–S306.
  • Church JA, Mitchell WG, Gonzalez-Gomez I, et al. Mitochondrial DNA depletion, near-fatal metabolic acidosis, and liver failure in an HIV-infected child treated with combination antiretroviral therapy. J Pediatr. 2001;138(5):748–751.
  • Alimenti A, Forbes JC, Oberlander TF, et al. A prospective controlled study of neurodevelopment in HIV-uninfected children exposed to combination antiretroviral drugs in pregnancy. Pediatrics. 2006;118(4):e1139–e1145.