Similar cortical morphometry trajectories from 5 to 9 years in children with perinatal HIV who started treatment before age 2 years and uninfected controls.
CHER
Children with HIV
Cortical thickness
FreeSurfer
Gyrification
Longitudinal
Vertex-wise
Journal
BMC neuroscience
ISSN: 1471-2202
Titre abrégé: BMC Neurosci
Pays: England
ID NLM: 100966986
Informations de publication
Date de publication:
24 02 2023
24 02 2023
Historique:
received:
25
10
2022
accepted:
14
02
2023
entrez:
24
2
2023
pubmed:
25
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection. 75 CHER participants in follow-up care at FAMCRU (Family Centre for Research with Ubuntu), as well as 66 age-matched controls, received magnetic resonance imaging (MRI) on a 3 T Siemens Allegra at ages 5, 7 and/or 9 years. MR images were processed, and cortical surfaces reconstructed using the FreeSurfer longitudinal processing stream. Vertex-wise linear mixed effects (LME) analyses were performed across the whole brain to compare the means and linear rates of change of cortical thickness and gyrification from 5 to 9 years between CPHIV and controls, as well as to examine effects of ART interruption. Children without HIV demonstrated generalized cortical thinning from 5 to 9 years, with the rate of thinning varying by region, as well as regional age-related gyrification increases. Overall, the means and developmental trajectories of cortical thickness and gyrification were similar in CPHIV. However, at an uncorrected p < 0.005, 6 regions were identified where the cortex of CPHIV was thicker than in uninfected children, namely bilateral insula, left supramarginal, lateral orbitofrontal and superior temporal, and right medial superior frontal regions. Planned ART interruption did not affect development of cortical morphometry. Although our results suggest that normal development of cortical morphometry between the ages of 5 and 9 years is preserved in CPHIV who started ART early, these findings require further confirmation with longitudinal follow-up through the vulnerable adolescent period.
Sections du résumé
BACKGROUND
Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection.
METHODS
75 CHER participants in follow-up care at FAMCRU (Family Centre for Research with Ubuntu), as well as 66 age-matched controls, received magnetic resonance imaging (MRI) on a 3 T Siemens Allegra at ages 5, 7 and/or 9 years. MR images were processed, and cortical surfaces reconstructed using the FreeSurfer longitudinal processing stream. Vertex-wise linear mixed effects (LME) analyses were performed across the whole brain to compare the means and linear rates of change of cortical thickness and gyrification from 5 to 9 years between CPHIV and controls, as well as to examine effects of ART interruption.
RESULTS
Children without HIV demonstrated generalized cortical thinning from 5 to 9 years, with the rate of thinning varying by region, as well as regional age-related gyrification increases. Overall, the means and developmental trajectories of cortical thickness and gyrification were similar in CPHIV. However, at an uncorrected p < 0.005, 6 regions were identified where the cortex of CPHIV was thicker than in uninfected children, namely bilateral insula, left supramarginal, lateral orbitofrontal and superior temporal, and right medial superior frontal regions. Planned ART interruption did not affect development of cortical morphometry.
CONCLUSIONS
Although our results suggest that normal development of cortical morphometry between the ages of 5 and 9 years is preserved in CPHIV who started ART early, these findings require further confirmation with longitudinal follow-up through the vulnerable adolescent period.
Identifiants
pubmed: 36829110
doi: 10.1186/s12868-023-00783-7
pii: 10.1186/s12868-023-00783-7
pmc: PMC9951512
doi:
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15Subventions
Organisme : NICHD NIH HHS
ID : R01 HD099846
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC015984
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD071664
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH108346
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH096559
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI053217
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
Références
UNAIDS. Global HIV & AIDS statistics—Fact sheet. 2022. Source: 2022. https://www.unaids.org/en/resources/fact-sheet . Accessed Aug 24.
Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008;359(21):2233–44.
pubmed: 19020325
pmcid: 2950021
doi: 10.1056/NEJMoa0800971
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):e681–93.
pubmed: 17296781
doi: 10.1542/peds.2006-1145
World Health Organization (WHO). Report of the WHO technical reference group. Paediatric HIV/ART care guideline group meeting. Geneva: WHO Headquarter; 2008.
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.
pubmed: 17137813
doi: 10.1016/j.ejpn.2006.10.006
Laughton B, Cornell M, Kidd M, Springer PE, Dobbels EFMT, Rensburg AJV, et al. Five year neurodevelopment outcomes of perinatally HIV-infected children on early limited or deferred continuous antiretroviral therapy. J Int AIDS Soc. 2018;21(5):e25106.
pubmed: 29722482
pmcid: 5932637
doi: 10.1002/jia2.25106
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.
pubmed: 23782482
pmcid: 3687073
doi: 10.7448/IAS.16.1.18603
Laughton B, Cornell M, Grove D, Kidd M, Springer PE, Dobbels E, et al. Early antiretroviral therapy improves neurodevelopmental outcomes in infants. AIDS (London, England). 2012;26(13):1685.
pubmed: 22614886
doi: 10.1097/QAD.0b013e328355d0ce
Randall SR, Warton CM, Holmes MJ, Cotton MF, Laughton B, van der Kouwe AJ, et al. Larger subcortical gray matter structures and smaller corpora callosa at age 5 years in HIV infected children on early ART. Front Neuroanat. 2017;11:95.
pubmed: 29163068
pmcid: 5673662
doi: 10.3389/fnana.2017.00095
Nwosu EC, Robertson FC, Holmes MJ, Cotton MF, Dobbels E, Little F, et al. Altered brain morphometry in 7-year old HIV-infected children on early ART. Metab Brain Dis. 2018;33(2):523–35.
pubmed: 29209922
doi: 10.1007/s11011-017-0162-6
Nwosu EC, Holmes MJ, Cotton MF, Dobbels E, Little F, Laughton B, et al. Cortical structural changes related to early antiretroviral therapy (ART) interruption in perinatally HIV-infected children at 5 years of age. IBRO Neuroscience Reports. 2021;10:161–70.
pubmed: 34179869
pmcid: 8211921
doi: 10.1016/j.ibneur.2021.02.001
Mbugua KK, Holmes MJ, Cotton MF, Ratai EM, Little F, Hess AT, et al. HIV-associated CD4/8 depletion in infancy is associated with neurometabolic reductions in the basal ganglia at age 5 years despite early antiretroviral therapy. AIDS. 2016;30(9):1353.
pubmed: 26959509
doi: 10.1097/QAD.0000000000001082
Robertson FC, Holmes MJ, Cotton MF, Dobbels E, Little F, Laughton B, et al. Perinatal HIV infection or exposure is associated with low N-acetylaspartate and glutamate in Basal Ganglia at age 9 but not 7 Years. Front Hum Neurosci. 2018;12:145.
pubmed: 29867401
pmcid: 5949349
doi: 10.3389/fnhum.2018.00145
Graham AS, Holmes MJ, Little F, Dobbels E, Cotton MF, Laughton B, et al. MRS suggests multi-regional inflammation and white matter axonal damage at 11 years following perinatal HIV infection. Neuro Image Clin. 2020;28:102505.
Ackermann C, Andronikou S, Saleh MG, Laughton B, Alhamud AA, van der Kouwe A, et al. Early antiretroviral therapy in HIV-infected children is associated with diffuse white matter structural abnormality and corpus callosum sparing. Am J Neuroradiol. 2016;37(12):2363–9.
pubmed: 27538904
pmcid: 5161701
doi: 10.3174/ajnr.A4921
Jankiewicz M, Holmes MJ, Taylor PA, Cotton MF, Laughton B, van der Kouwe AJ, et al. White matter abnormalities in children with HIV infection and exposure. Front Neuroanat. 2017;11:1662–5129. https://doi.org/10.3389/fnana.2017.00088 .
doi: 10.3389/fnana.2017.00088
Li JZ, Smith DM, Mellors JW. The critical roles of treatment interruption studies and biomarker identification in the search for an HIV cure. AIDS. 2015;29(12):1429.
pubmed: 25870989
doi: 10.1097/QAD.0000000000000658
Dubrocq G, Rakhmanina N. Antiretroviral therapy interruptions: impact on HIV treatment and transmission. HIV/AIDS. 2018;10:91.
Wamalwa D, Benki-Nugent S, Langat A, Tapia K, Ngugi E, Moraa H, et al. Treatment interruption after 2-year antiretroviral treatment initiated during acute/early HIV in infancy. AIDS. 2016;30(15):2303–13.
pubmed: 27177316
doi: 10.1097/QAD.0000000000001158
Ananworanich J, Melvin D, Amador JT, Childs T, Medin G, Boscolo V, et al. Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption. AIDS. 2016;30(7):1075–81.
pubmed: 26730569
doi: 10.1097/QAD.0000000000001011
Lewis J, Payne H, Walker AS, Otwombe K, Gibb DM, Babiker AG, et al. Thymic output and CD4 T-cell reconstitution in HIV-infected children on early and interrupted antiretroviral treatment: evidence from the children with HIV early antiretroviral therapy trial. Front Immunol. 2017;8:1162.
pubmed: 28979264
pmcid: 5611383
doi: 10.3389/fimmu.2017.01162
Shaw P, Kabani NJ, Lerch JP, Eckstrand K, Lenroot R, Gogtay N, et al. Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci. 2008;28(14):3586–94.
pubmed: 18385317
pmcid: 6671079
doi: 10.1523/JNEUROSCI.5309-07.2008
Reuter M, Schmansky NJ, Rosas HD, Fischl B. Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage. 2012;61(4):1402–18.
pubmed: 22430496
doi: 10.1016/j.neuroimage.2012.02.084
Van Biljon N, Robertson F, Holmes M, Cotton MF, Laughton B, van der Kouwe A, et al. Multivariate approach for longitudinal analysis of brain metabolite levels from ages 5–11 years in children with perinatal HIV infection. Neuroimage. 2021;237:118101.
pubmed: 33961998
doi: 10.1016/j.neuroimage.2021.118101
Moeskops P, Benders MJ, Kersbergen KJ, Groenendaal F, de Vries LS, Viergever MA, et al. Development of cortical morphology evaluated with longitudinal MR brain images of preterm infants. PLoS ONE. 2015;10(7):e0131552.
pubmed: 26161536
pmcid: 4498793
doi: 10.1371/journal.pone.0131552
Mills KL, Tamnes CK. Methods and considerations for longitudinal structural brain imaging analysis across development. Dev Cogn Neurosci. 2014;9:172–90.
pubmed: 24879112
pmcid: 6989768
doi: 10.1016/j.dcn.2014.04.004
Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci. 2000;97(20):11050–5.
pubmed: 10984517
pmcid: 27146
doi: 10.1073/pnas.200033797
Cao B, Mwangi B, Passos IC, Wu MJ, Keser Z, Zunta-Soares GB, et al. Lifespan gyrification trajectories of human brain in healthy individuals and patients with major psychiatric disorders. Sci Rep. 2017;7(1):511.
pubmed: 28360420
pmcid: 5428697
doi: 10.1038/s41598-017-00582-1
Li G, Wang L, Shi F, Lyall AE, Lin W, Gilmore JH, et al. Mapping longitudinal development of local cortical gyrification in infants from birth to 2 years of age. J Neurosci. 2014;34(12):4228–38.
pubmed: 24647943
pmcid: 3960466
doi: 10.1523/JNEUROSCI.3976-13.2014
Lebel C, Beaulieu C. Longitudinal development of human brain wiring continues from childhood into adulthood. J Neurosci. 2011;31(30):10937–47.
pubmed: 21795544
pmcid: 6623097
doi: 10.1523/JNEUROSCI.5302-10.2011
Aubert-Broche B, Fonov VS, García-Lorenzo D, Mouiha A, Guizard N, Coupé P, et al. A new method for structural volume analysis of longitudinal brain MRI data and its application in studying the growth trajectories of anatomical brain structures in childhood. Neuroimage. 2013;82:393–402.
pubmed: 23719155
doi: 10.1016/j.neuroimage.2013.05.065
Tamnes CK, Walhovd KB, Dale AM, Østby Y, Grydeland H, Richardson G, et al. Brain development and aging: overlapping and unique patterns of change. Neuroimage. 2013;68:63–74.
pubmed: 23246860
doi: 10.1016/j.neuroimage.2012.11.039
World Health Organization (WHO). Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access. Recommendations for a public health approach. 2006. Source: http://www.who.int/hiv/pub/guidelines/WHOpaediatric.pdf . Accessed 12 October, 2017.
Cotton MF, Violari A, Otwombe K, Panchia R, Dobbels E, Rabie H, et al. Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial. Lancet. 2013;382(9904):1555–63. https://doi.org/10.1016/S0140-6736(13)61409-9 .
doi: 10.1016/S0140-6736(13)61409-9
pubmed: 24209829
pmcid: 4104982
Madhi SA, Adrian P, Cotton MF, McIntyre JA, Jean-Philippe P, Meadows S, et al. Effect of HIV infection status and anti-retroviral treatment on quantitative and qualitative antibody responses to pneumococcal conjugate vaccine in infants. J Infect Dis. 2010;202(3):355–61.
pubmed: 20583920
doi: 10.1086/653704
van Wyhe KS, Laughton B, Cotton MF, Meintjes EM, van der Kouwe AJ, Boivin MJ, et al. Cognitive outcomes at ages seven and nine years in South African children from the children with HIV early antiretroviral (CHER) trial: a longitudinal investigation. J Int AIDS Soc. 2021;24(7):e25734.
pubmed: 34259393
pmcid: 8278859
doi: 10.1002/jia2.25734
Tisdall MD, Hess AT, Reuter M, Meintjes EM, Fischl B, van der Kouwe AJ. Volumetric navigators for prospective motion correction and selective reacquisition in neuroanatomical MRI. Magn Reson Med. 2012;68(2):389–99.
pubmed: 22213578
doi: 10.1002/mrm.23228
Van der Kouwe AJ, Benner T, Salat DH, Fischl B. Brain morphometry with multiecho MPRAGE. Neuroimage. 2008;40(2):559–69.
pubmed: 18242102
doi: 10.1016/j.neuroimage.2007.12.025
Reuter M, Rosas HD, Fischl B. Highly accurate inverse consistent registration: a robust approach. Neuroimage. 2010;53(4):1181–96.
pubmed: 20637289
doi: 10.1016/j.neuroimage.2010.07.020
Reuter M, Fischl B. Avoiding asymmetry-induced bias in longitudinal image processing. Neuroimage. 2011;57(1):19–21.
pubmed: 21376812
doi: 10.1016/j.neuroimage.2011.02.076
Bernal-Rusiel JL, Greve DN, Reuter M, Fischl B, Sabuncu MR. Alzheimer’s disease neuroimaging initiative. Statistical analysis of longitudinal neuroimage data with linear mixed effects models. Neuroimage. 2013;66:249–60.
pubmed: 23123680
doi: 10.1016/j.neuroimage.2012.10.065
Sowell ER, Thompson PM, Leonard CM, Welcome SE, Kan E, Toga AW. Longitudinal mapping of cortical thickness and brain growth in normal children. J Neurosci. 2004;24(38):8223–31.
pubmed: 15385605
pmcid: 6729679
doi: 10.1523/JNEUROSCI.1798-04.2004
Raznahan A, Shaw P, Lalonde F, Stockman M, Wallace GL, Greenstein D, et al. How does your cortex grow? J Neurosci. 2011;31(19):7174–7.
pubmed: 21562281
pmcid: 3157294
doi: 10.1523/JNEUROSCI.0054-11.2011
Ducharme S, Albaugh MD, Nguyen TV, Hudziak JJ, Mateos-Pérez JM, Labbe A, et al. Trajectories of cortical thickness maturation in normal brain development—the importance of quality control procedures. Neuroimage. 2016;125:267–79.
pubmed: 26463175
doi: 10.1016/j.neuroimage.2015.10.010
Schnack HG, Van Haren NE, Brouwer RM, Evans A, Durston S, Boomsma DI, et al. Changes in thickness and surface area of the human cortex and their relationship with intelligence. Cereb Cortex. 2015;25(6):1608–17.
pubmed: 24408955
doi: 10.1093/cercor/bht357
Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW. Mapping cortical change across the human life span. Nat Neurosci. 2003;6(3):309.
pubmed: 12548289
doi: 10.1038/nn1008
White T, Su S, Schmidt M, Kao CY, Sapiro G. The development of gyrification in childhood and adolescence. Brain Cogn. 2010;72(1):36–45.
pubmed: 19942335
doi: 10.1016/j.bandc.2009.10.009
Santos E, Noggle CA. Synaptic pruning. In: Goldstein S, Naglieri JA, editors. Encyclopedia of child behavior and development. Boston: Springer; 2011.
Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci. 2004;101(21):8174–9.
pubmed: 15148381
pmcid: 419576
doi: 10.1073/pnas.0402680101
Huizinga M, Dolan CV, van der Molen MW. Age-related change in executive function: developmental trends and a latent variable analysis. Neuropsychologia. 2006;44(11):2017–36.
pubmed: 16527316
doi: 10.1016/j.neuropsychologia.2006.01.010
Diamond A. Normal development of prefrontal cortex from birth to young adulthood: cognitive functions, anatomy, and biochemistry. In: Stuss D, Knight R, editors. Principles of frontal lobe function. New York: Oxford University Press; 2002. p. 466–503.
doi: 10.1093/acprof:oso/9780195134971.003.0029
Van Essen DC. A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature. 1997;385(6614):313.
pubmed: 9002514
doi: 10.1038/385313a0
Chung YS, Hyatt CJ, Stevens MC. Adolescent maturation of the relationship between cortical gyrification and cognitive ability. Neuroimage. 2017;158:319–31.
pubmed: 28676299
doi: 10.1016/j.neuroimage.2017.06.082
Kersbergen KJ, Leroy F, Išgum I, Groenendaal F, de Vries LS, Claessens NH, et al. Relation between clinical risk factors, early cortical changes, and neurodevelopmental outcome in preterm infants. Neuroimage. 2016;142:301–10.
pubmed: 27395393
doi: 10.1016/j.neuroimage.2016.07.010
Blanton RE, Levitt JG, Thompson PM, Narr KL, Capetillo-Cunliffe L, Nobel A, et al. Mapping cortical asymmetry and complexity patterns in normal children. Psychiatr Res Neuroimaging. 2001;107(1):29–43.
doi: 10.1016/S0925-4927(01)00091-9
Lewis-de Los Angeles CP, Williams PL, Jenkins LM, Huo Y, Malee K, Alpert KI, et al. Brain morphometric differences in youth with and without perinatally-acquired HIV: a cross-sectional study. NeuroImage Clinical. 2020;26:102246. https://doi.org/10.1016/j.nicl.2020.102246 .
doi: 10.1016/j.nicl.2020.102246
pubmed: 32251906
pmcid: 7132093
Yu X, Gao L. Neuroanatomical changes underlying vertical HIV infection in adolescents. Front Immunol. 2019;10:814. https://doi.org/10.3389/fimmu.2019.00814 .
doi: 10.3389/fimmu.2019.00814
pubmed: 31110499
pmcid: 6499204
Yadav SK, Gupta RK, Garg RK, Venkatesh V, Gupta PK, Singh AK, et al. Altered structural brain changes and neurocognitive performance in pediatric HIV. Neuro Image Clin. 2017;14:316–22.
Hoare J, Fouche JP, Phillips N, Joska JA, Myer L, Zar HJ, et al. Structural brain changes in perinatally HIV-infected young adolescents in South Africa. AIDS. 2018;32(18):2707–18.
pubmed: 30234601
doi: 10.1097/QAD.0000000000002024
Van den Hof M, Jellema PE, Ter Haar AM, Scherpbier HJ, Schrantee A, Kaiser A, Caan MW, Majoie CB, Reiss P, Wit FW, Mutsaerts HJ. Normal structural brain development in adolescents treated for perinatally acquired HIV: a longitudinal imaging study. AIDS. 2021;35(8):1221.
pubmed: 33710018
doi: 10.1097/QAD.0000000000002873
Wade BS, Valcour VG, Puthanakit T, Saremi A, Gutman BA, Nir TM, Watson C, Aurpibul L, Kosalaraksa P, Ounchanum P, Kerr S. Mapping abnormal subcortical neurodevelopment in a cohort of Thai children with HIV. NeuroImage Clin. 2019;23:101810.
pubmed: 31029050
pmcid: 6482384
doi: 10.1016/j.nicl.2019.101810
Bunupuradah T, Duong T, Compagnucci A, McMaster P, Bernardi S, Kanjanavanit S, et al. Outcomes after reinitiating antiretroviral therapy in children randomized to planned treatment interruptions. AIDS. 2013;27(4):579–89.
pubmed: 23135172
doi: 10.1097/QAD.0b013e32835c1181
Montserrat M, Plana M, Guardo AC, Andrés C, Climent N, Gallart T, et al. Impact of long-term antiretroviral therapy interruption and resumption on viral reservoir in HIV-1 infected patients. AIDS. 2017;31(13):1895–7.
pubmed: 28590333
doi: 10.1097/QAD.0000000000001560
Donald KA, Hoare J, Eley B, Wilmshurst JM. Neurologic complications of pediatric human immunodeficiency virus: implications for clinical practice and management challenges in the African setting. Semin Pediatr Neurol. 2014;21(1):3–11. https://doi.org/10.1016/j.spen.2014.01.004 .
doi: 10.1016/j.spen.2014.01.004
pubmed: 24655398
Chriboga 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):402–7.
doi: 10.1016/j.jpeds.2004.10.021
Foster CJ, Biggs RL, Melvin D, Walters MDS, Tudor-Williams G, Lyall EGH. Neurodevelopmental outcomes in children with HIV infection under 3 years of age. Dev Med Child Neurol. 2006;48(8):677–82.
pubmed: 16836781
doi: 10.1017/S0012162206001423
Lobato MN, Caldwell MB, Ng P, Oxtoby MJ. Pediatric spectrum of disease clinical consortium. Encephalopathy in children with perinatally acquired human immunodeficiency virus infection. J Pediatr. 1995;126(5):710–5.
pubmed: 7751993
doi: 10.1016/S0022-3476(95)70397-7