Top

Published in:

Open Access 01-02-2022 | Human Immunodeficiency Virus | Central Nervous System and Cognition (SS Spudich, Section Editor)

Central Nervous System Impact of Perinatally Acquired HIV in Adolescents and Adults: an Update

Author: Sharon L. Nichols

Published in: Current HIV/AIDS Reports | Issue 1/2022

Abstract

Purpose of Review

Perinatally acquired HIV infection (PHIV) can confer neurodevelopmental risk. As children with PHIV increasingly survive through adolescence and into adulthood, understanding its long-term central nervous system (CNS) impacts is critical for maximizing adult outcomes and quality of life.

Recent Findings

Recently published neurocognitive and neuroimaging findings show impacts on the CNS associated with early HIV disease progression that endure into adolescence and young adulthood. Although developmental trajectories in adolescence largely appear stable, further research on maturational processes is indicated.

Summary

Although early antiretroviral therapy in infancy appears to be protective, it is not universally available and current youth largely developed without its benefit. The neurocognitive effects of HIV and the multiple other risks to neurodevelopment experienced by youth with PHIV call for further longitudinal research and a multifaceted approach to prevention and intervention.

UNICEF. Global and regional trends. 2020.

UNAIDS. Fact Sheet 2021: Global HIV Statistics. 2021.

Slogrove AL, Sohn AH. The global epidemiology of adolescents living with HIV: time for more granular data to improve adolescent health outcomes. Curr Opin HIV AIDS. 2018;13(3):170–8. https://doi.org/10.1097/coh.0000000000000449.CrossRefPubMedPubMedCentral

Vreeman RC, Rakhmanina NY, Nyandiko WM, Puthanakit T, Kantor R. Are we there yet? 40 years of successes and challenges for children and adolescents living with HIV. J Int AIDS Soc. 2021;24(6):e25759. https://doi.org/10.1002/jia2.25759.CrossRefPubMedPubMedCentral

Smith R, Wilkins M. Perinatally acquired HIV infection: long-term neuropsychological consequences and challenges ahead. Child Neuropsychol. 2015;21(2):234–68. https://doi.org/10.1080/09297049.2014.898744.CrossRefPubMed

Sillman B, Woldstad C, McMillan J, Gendelman HE. Neuropathogenesis of human immunodeficiency virus infection. Handb Clin Neurol. 2018;152:21–40. https://doi.org/10.1016/b978-0-444-63849-6.00003-7.CrossRefPubMed

Spudich S, Peterson J, Fuchs D, Price RW, Gisslen M. Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence. AIDS (London, England). 2019;33(Suppl 2):S135-s44. https://doi.org/10.1097/qad.0000000000002326.CrossRef

Rowe K, Buivydaite R, Heinsohn T, Rahimzadeh M, Wagner RG, Scerif G, et al. Executive function in HIV-affected children and adolescents: a systematic review and meta-analyses. AIDS Care. 2021:1–25 https://doi.org/10.1080/09540121.2021.1873232.

Bartlett AW, Williams PCM, Jantarabenjakul W, Kerr SJ. State of the mind: growing up with HIV. Paediatr Drugs. 2020;22(5):511–24. https://doi.org/10.1007/s40272-020-00415-1.CrossRefPubMed

10.

Benki-Nugent S, Boivin MJ. Neurocognitive complications of pediatric HIV infections. Curr Top Behav Neurosci. 2019. https://doi.org/10.1007/7854_2019_102.CrossRef

11.

Phillips N, Amos T, Kuo C, Hoare J, Ipser J, Thomas KG, et al. HIV-Associated cognitive impairment in perinatally infected children: a meta-analysis. Pediatrics. 2016;138(5) https://doi.org/10.1542/peds.2016-0893.

12.

Wilmshurst JM, Hammond CK, Donald K, Hoare J, Cohen K, Eley B. NeuroAIDS in children. Handb Clin Neurol. 2018;152:99–116. https://doi.org/10.1016/b978-0-444-63849-6.00008-6.CrossRefPubMed

13.

Van den Hof M, Ter Haar AM, Caan MWA, Spijker R, van der Lee JH, Pajkrt D. Brain structure of perinatally HIV-infected patients on long-term treatment: a systematic review. Neurol Clin Pract. 2019;9(5):433–42. https://doi.org/10.1212/cpj.0000000000000637.CrossRefPubMedPubMedCentral

14.

Musielak K, Fine J. An updated systematic review of neuroimaging studies of children and adolescent with perinatally acquired HIV. J Pediatr Neuropsychol. 2016;2:34–49. https://doi.org/10.1007/s40817-015-0009-1.CrossRef

15.

Martín-Bejarano M, Ruiz-Saez B, Martinez-de-Aragón A, Melero H, Zamora B, Malpica NA, et al. A systematic review of magnetic resonance imaging studies in perinatally HIV-infected individuals. AIDS Rev. 2021. https://doi.org/10.24875/AIDSRev.20000088.CrossRefPubMed

16.

Thakur KT, Boubour A, Saylor D, Das M, Bearden DR, Birbeck GL. Global HIV neurology: a comprehensive review. AIDS (London, England). 2019;33(2):163–84. https://doi.org/10.1097/qad.0000000000001796.CrossRef

17.

Ezeamama AE, Zalwango SK, Sikorskii A, Tuke R, Musoke PM, Giordani B, et al. In utero and peripartum antiretroviral exposure as predictor of cognition in 6- to 10-year-old HIV-exposed Ugandan children - a prospective cohort study. HIV Med. 2021. https://doi.org/10.1111/hiv.13094.CrossRefPubMedPubMedCentral

18.

Kerr SJ, Puthanakit T, Vibol U, Aurpibul L, Vonthanak S, Kosalaraksa P, et al. Neurodevelopmental outcomes in HIV-exposed-uninfected children versus those not exposed to HIV. AIDS Care. 2014;26(11):1327–35. https://doi.org/10.1080/09540121.2014.920949.CrossRefPubMedPubMedCentral

19.

McHenry MS, Balogun KA, McDonald BC, Vreeman RC, Whipple EC, Serghides L. In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes. J Int AIDS Soc. 2019;22(4):e25275. https://doi.org/10.1002/jia2.25275.CrossRefPubMedPubMedCentral

20.

Centers for Disease Control. Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Morb Mortal Wkly Rep. 1994;43:1–12.

21.

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. https://doi.org/10.7448/ias.16.1.18603.CrossRefPubMedPubMedCentral

22.

Smith R, Chernoff M, Williams PL, Malee KM, Sirois PA, Kammerer B, et al. Impact of HIV severity on cognitive and adaptive functioning during childhood and adolescence. Pediatr Infect Dis J. 2012;31(6):592–8. https://doi.org/10.1097/INF.0b013e318253844b.CrossRefPubMed

23.

Crowell CS, Huo Y, Tassiopoulos K, Malee KM, Yogev R, Hazra R, et al. Early viral suppression improves neurocognitive outcomes in HIV-infected children. AIDS (London, England). 2015;29(3):295–304. https://doi.org/10.1097/qad.0000000000000528.CrossRef

24.

Jantarabenjakul W, Chonchaiya W, Puthanakit T, Theerawit T, Payapanon J, Sophonphan J, et al. Low risk of neurodevelopmental impairment among perinatally acquired HIV-infected preschool children who received early antiretroviral treatment in Thailand. J Int AIDS Soc. 2019;22(4):e25278. https://doi.org/10.1002/jia2.25278.CrossRefPubMedPubMedCentral

25.

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):1685–90. https://doi.org/10.1097/QAD.0b013e328355d0ce.CrossRef

26.

Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Available at https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/PediatricGuidelines.pdf. Accessed 17 Jan 2022.

27.

Slogrove AL, Schomaker M, Davies MA, Williams P, Balkan S, Ben-Farhat J, et al. The epidemiology of adolescents living with perinatally acquired HIV: a cross-region global cohort analysis. PLoS Med. 2018;15(3):e1002514. https://doi.org/10.1371/journal.pmed.1002514.CrossRefPubMedPubMedCentral

28.

Frigati LJ, Brown K, Mahtab S, Githinji L, Gray D, Zühlke L, et al. Multisystem impairment in South African adolescents with Perinatally acquired HIV on antiretroviral therapy (ART). J Int AIDS Soc. 2019;22(8):e25386. https://doi.org/10.1002/jia2.25386.CrossRefPubMedPubMedCentral

29.

Flynn PM, Abrams EJ. Growing up with perinatal HIV. AIDS (London, England). 2019;33(4):597–603. https://doi.org/10.1097/qad.0000000000002092.CrossRef

30.

Sirois PA, Chernoff MC, Malee KM, Garvie PA, Harris LL, Williams PL, et al. Associations of memory and executive functioning with academic and adaptive functioning among youth with perinatal HIV exposure and/or infection. J Pediatr Infect Dis Soc. 2016;5(suppl 1):S24-s32. https://doi.org/10.1093/jpids/piw046.CrossRef

31.

Phillips N, Thomas KGF, Mtukushe B, Myer L, Zar HJ, Stein DJ, et al. Youth perinatal HIV-associated neurocognitive disorders: association with functional impairment. AIDS Care. 2021:1–5 https://doi.org/10.1080/09540121.2021.1891191.

32.

Garvie PA, Zeldow B, Malee K, Nichols SL, Smith RA, Wilkins ML, et al. Discordance of cognitive and academic achievement outcomes in youth with perinatal HIV exposure. Pediatr Infect Dis J. 2014;33(9):e232-8. https://doi.org/10.1097/inf.0000000000000314.CrossRefPubMedPubMedCentral

33.

Toska E, Cluver L, Orkin M, Bains A, Sherr L, Berezin M, et al. Screening and supporting through schools: educational experiences and needs of adolescents living with HIV in a South African cohort. BMC Public Health. 2019;19(1):272. https://doi.org/10.1186/s12889-019-6580-0.CrossRefPubMedPubMedCentral

34.

Mellins CA, Malee KM. Understanding the mental health of youth living with perinatal HIV infection: lessons learned and current challenges. J Int AIDS Soc. 2013;16(1):18593. https://doi.org/10.7448/ias.16.1.18593.CrossRefPubMedPubMedCentral

35.

Nichols SL, Brummel S, Malee KM, Mellins CA, Moscicki AB, Smith R, et al. The role of behavioral and neurocognitive functioning in substance use among youth with perinatally acquired HIV infection and perinatal HIV exposure without infection. AIDS Behav. 2021. https://doi.org/10.1007/s10461-021-03174-3.CrossRefPubMed

36.

Yusuf H, Agwu A. Adolescents and young adults with early acquired HIV infection in the united states: unique challenges in treatment and secondary prevention. Exp Rev Anti-Infect Ther. 2021;19(4):457–71. https://doi.org/10.1080/14787210.2021.1829473.CrossRef

37.

UNAIDS. Global AIDS update – Seizing the moment – Tackling entrenched inequalities to end epidemics. 2020. Available at https://www.unaids.org/en/resources/documents/2020/global-aids-report. Accessed 17 Jan 2022.

38.

World Health Organisation. Adolescent health. Available at https://www.who.int/health-topics/adolescent-health#tab=tab_1. Accessed 17 Jan 2022.

39.

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 Eradication. 2015;1(3):196–202.CrossRef

40.

Puthanakit T, Ananworanich J, Vonthanak S, Kosalaraksa P, Hansudewechakul R, van der Lugt J, 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):501–8. https://doi.org/10.1097/INF.0b013e31827fb19d.CrossRefPubMedPubMedCentral

41.

Tassiopoulos K, Patel K, Alperen J, Kacanek D, Ellis A, Berman C, et al. Following young people with perinatal HIV infection from adolescence into adulthood: the protocol for PHACS AMP Up, a prospective cohort study. BMJ Open. 2016;6(6):e011396. https://doi.org/10.1136/bmjopen-2016-011396.CrossRefPubMedPubMedCentral

42.

• Kerr SJ, Puthanakit T, Malee KM, Thongpibul K, Ly PS, Sophonphan J, et al. Increased risk of executive function and emotional behavioral problems among virologically well-controlled perinatally HIV-infected adolescents in Thailand and Cambodia. J Acquir Immune Defic Syndr. 2019;82(3):297–304. https://doi.org/10.1097/qai.0000000000002132. This study is important in describing cognitive functioning among a cohort of youth with relatively well controlled HIV during development.

43.

Patel PB, Belden A, Handoko R, Puthanakit T, Kerr S, Kosalaraksa P, et al. Behavioral impairment and cognition in Thai adolescents affected by HIV. Glob Mental Health (Cambridge, England). 2021;8: e3. https://doi.org/10.1017/gmh.2021.1.CrossRef

44.

Malee KM, Chernoff MC, Sirois PA, Williams PL, Garvie PA, Kammerer BL, et al. Impact of perinatally acquired HIV disease upon longitudinal changes in memory and executive functioning. J Acquir Immune Defic Syndr (1999). 2017;75(4):455–64. https://doi.org/10.1097/qai.0000000000001441.CrossRef

45.

Nichols SL, Chernoff MC, Malee K, Sirois PA, Williams PL, Figueroa V, et al. Learning and memory in children and adolescents with perinatal HIV infection and perinatal HIV exposure. Pediatr Infect Dis J. 2016;35(6):649–54. https://doi.org/10.1097/inf.0000000000001131.CrossRefPubMedPubMedCentral

46.

Harris LL, Chernoff MC, Nichols SL, Williams PL, Garvie PA, Yildirim C, et al. Prospective memory in youth with perinatally-acquired HIV infection. Child Neuropsychol. 2018;24(7):938–58. https://doi.org/10.1080/09297049.2017.1360854.CrossRefPubMed

47.

Nichols SL, Chernoff MC, Malee KM, Sirois PA, Woods SP, Williams PL, et al. Executive functioning in children and adolescents with perinatal HIV infection and perinatal HIV exposure. J Pediatr Infect Dis Soc. 2016;5(suppl 1):S15-s23. https://doi.org/10.1093/jpids/piw049.CrossRef

48.

Nichols SL, Brummel SS, Smith RA, Garvie PA, Hunter SJ, Malee KM, et al. Executive functioning in children and adolescents with perinatal HIV infection. Pediatr Infect Dis J. 2015;34(9):969–75. https://doi.org/10.1097/inf.0000000000000809.CrossRefPubMedPubMedCentral

49.

Van den Hof M, Ter Haar AM, Scherpbier HJ, van der Lee JH, Reiss P, Wit F, et al. Neurocognitive development in perinatally human immunodeficiency virus-infected adolescents on long-term treatment, compared to healthy matched controls: a longitudinal study. Clin Infect Dis. 2020;70(7):1364–71. https://doi.org/10.1093/cid/ciz386.CrossRefPubMed

50.

Patel PB, Apornpong T, Puthanakit T, Thongpibul K, Kosalaraksa P, Hansudewechakul R, et al. Trajectory analysis of cognitive outcomes in children with perinatal HIV. Pediatr Infect Dis J. 2019;38(10):1038–44. https://doi.org/10.1097/inf.0000000000002427.CrossRefPubMedPubMedCentral

51.

Judd A, Le Prevost M, Melvin D, Arenas-Pinto A, Parrott F, Winston A, et al. Cognitive function in young persons with and without perinatal HIV in the AALPHI cohort in England: role of non-HIV-related factors. Clin Infect Dis. 2016;63(10):1380–7. https://doi.org/10.1093/cid/ciw568.CrossRefPubMedPubMedCentral

52.

• Robbins RN, Zimmerman R, Korich R, Raymond J, Dolezal C, Choi CJ, et al. Longitudinal trajectories of neurocognitive test performance among individuals with perinatal HIV-infection and -exposure: adolescence through young adulthood. AIDS Care. 2020;32(1):21–9. https://doi.org/10.1080/09540121.2019.1626343. This study highlights processing speed as a potential area of risk over time for youth with PHIV.

53.

Willen EJ, Cuadra A, Arheart KL, Post MJ, Govind V. Young adults perinatally infected with HIV perform more poorly on measures of executive functioning and motor speed than ethnically matched healthy controls. AIDS Care. 2017;29(3):387–93. https://doi.org/10.1080/09540121.2016.1234677.CrossRefPubMed

54.

García-Navarro C, Jimenez de Ory S, Velo Higueras C, Zamora B, Prieto L, Ramos JT, et al. Significant differences between verbal and non-verbal intellectual scales on a perinatally HIV-infected cohort: from pediatrics to young adults. Heliyon. 2020;6(4):e03600 https://doi.org/10.1016/j.heliyon.2020.e03600.

55.

Coutifaris P, Byrd D, Childs J, Clark U, Posada R, Robbins R, et al. Neurobehavioral outcomes in young adults with perinatally acquired HIV. AIDS (London, England). 2020;34(14):2081–8. https://doi.org/10.1097/qad.0000000000002655.CrossRef

56.

Obregon-Perko V, Bricker K, Chahroudi A. The brain retains: nonhuman primate models for pediatric HIV-1 in the CNS. Curr HIV/AIDS Rep. 2020;17(4):343–53. https://doi.org/10.1007/s11904-020-00503-4.CrossRefPubMedPubMedCentral

57.

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):221–9. https://doi.org/10.1007/s11011-013-9456-5.CrossRefPubMed

58.

Li J, Gao L, Wen Z, Zhang J, Wang P, Tu N, et al. Structural covariance of gray matter volume in HIV vertically infected adolescents. Sci Rep. 2018;8(1):1182. https://doi.org/10.1038/s41598-018-19290-5.CrossRefPubMedPubMedCentral

59.

Li J, Gao L, Ye Z. Study of brain structure in HIV vertically infected adolescents. AIDS Res Hum Retrovir. 2021. https://doi.org/10.1089/aid.2020.0030.CrossRefPubMedPubMedCentral

60.

Yu X, Gao L, Wang H, Yin Z, Fang J, Chen J, et al. Neuroanatomical changes underlying vertical HIV infection in adolescents. Front Immunol. 2019;10:814. https://doi.org/10.3389/fimmu.2019.00814.CrossRefPubMedPubMedCentral

61.

Sarma MK, Keller MA, Macey PM, Michalik DE, Hayes J, Nielsen-Saines K, et al. White matter microstructure among perinatally HIV-infected youth: a diffusion tensor imaging study. J Neurovirol. 2019;25(3):313–23. https://doi.org/10.1007/s13365-018-0714-5.CrossRefPubMedPubMedCentral

62.

Ruiz-Saez B, García MM, de Aragon AM, Gil-Correa M, Melero H, Malpica NA, et al. Effects of perinatal HIV-infection on the cortical thickness and subcortical gray matter volumes in young adulthood. Medicine. 2021;100(15):e25403. https://doi.org/10.1097/md.0000000000025403.CrossRefPubMedPubMedCentral

63.

Lewis-de Los Angeles CP, Alpert KI, Williams PL, Malee K, Huo Y, Csernansky JG, et al. Deformed subcortical structures are related to past HIV disease severity in youth with perinatally acquired HIV infection. J Pediatr Infect Dis Soc. 2016;5(suppl 1):S6–s14 https://doi.org/10.1093/jpids/piw051.

64.

Lewis-de Los Angeles CP, Williams PL, Huo Y, Wang SD, Uban KA, Herting MM, et al. Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection: associations with HIV disease severity, substance use, and cognition. Brain Behav Immun. 2017;62:100–109 https://doi.org/10.1016/j.bbi.2017.01.004.

65.

• 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 Clin. 2020;26:102246 https://doi.org/10.1016/j.nicl.2020.102246. This study presents intriguing findings suggesting possible alterations in maturational cortical pruning in the context of PHIV.

66.

Hoare J, Myer L, Heany S, Fouche JP, Phillips N, Zar HJ, et al. Cognition, structural brain changes, and systemic inflammation in adolescents living with HIV on antiretroviral therapy. J Acquir Immune Defic Syndr (1999). 2020;84(1):114–121 https://doi.org/10.1097/qai.0000000000002314.

67.

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. https://doi.org/10.1007/s11011-017-0162-6.CrossRefPubMed

68.

Casagrande CC, Lew BJ, Taylor BK, Schantell M, O’Neill J, May PE, et al. Impact of HIV-infection on human somatosensory processing, spontaneous cortical activity, and cortical thickness: a multimodal neuroimaging approach. Hum Brain Mapp. 2021;42(9):2851–61. https://doi.org/10.1002/hbm.25408.

69.

Kapetanovic S, Norato G, Nair G, Julnes PS, Traino KA, Geannopoulos K, et al. Effect of HIV and interpersonal trauma on cortical thickness, cognition, and daily functioning. J Acquir Immune Defic Syndr (1999). 2020;84(4):405–413 https://doi.org/10.1097/qai.0000000000002358.

70.

MacDuffie KE, Brown GG, McKenna BS, Liu TT, Meloy MJ, Tawa B, et al. Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume. NeuroImage Clin. 2018;20:1044–52. https://doi.org/10.1016/j.nicl.2018.09.034.CrossRefPubMedPubMedCentral

71.

Williams ME, Joska JA, Amod AR, Paul RH, Stein DJ, Ipser JC, et al. The association of peripheral immune markers with brain cortical thickness and surface area in South African people living with HIV. J Neurovirol. 2020;26(6):908–19. https://doi.org/10.1007/s13365-020-00873-w.CrossRefPubMed

72.

Zhao J, Ma Z, Chen F, Li L, Ren M, Li A, et al. Human immune deficiency virus-related structural alterations in the brain are dependent on age. Hum Brain Mapp. 2021;42(10):3131–40. https://doi.org/10.1002/hbm.25423.CrossRefPubMedPubMedCentral

73.

Dean O, Buda A, Adams HR, Mwanza-Kabaghe S, Potchen MJ, Mbewe EG, et al. Brain magnetic resonance imaging findings associated with cognitive impairment in children and adolescents with human immunodeficiency virus in Zambia. Pediatr Neurol. 2020;102:28–35. https://doi.org/10.1016/j.pediatrneurol.2019.08.014.CrossRefPubMed

74.

Wade BSC, Valcour VG, Puthanakit T, Saremi A, Gutman BA, Nir TM, et al. Mapping abnormal subcortical neurodevelopment in a cohort of Thai children with HIV. NeuroImage Clin. 2019;23:101810. https://doi.org/10.1016/j.nicl.2019.101810.CrossRefPubMedPubMedCentral

75.

Van den Hof M, Jellema PEJ, Haar AMT, Scherpbier HJ, Schrantee A, Kaiser A, et al. Normal structural brain development in adolescents treated for perinatally acquired HIV: a longitudinal imaging study. AIDS (London, England). 2021 https://doi.org/10.1097/qad.0000000000002873.

76.

• Hoare J, Stein DJ, Heany SJ, Fouche JP, Phillips N, Er S, et al. Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures. J Neurovirol. 2021. https://doi.org/10.1007/s13365-021-00947-3. This recent neuroimaging study of young adolescents with PHIV raises the issue of the impact of epigenetic aging on brain development in this cohort.

77.

Horvath S, Stein DJ, Phillips N, Heany SJ, Kobor MS, Lin DTS, et al. Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents. AIDS (London, England). 2018;32(11):1465–74. https://doi.org/10.1097/qad.0000000000001854.CrossRef

78.

Shiau S, Cantos A, Ramon CV, Shen Y, Shah J, Jang G, et al. Epigenetic age in young African American adults with perinatally-acquired HIV. J Acquir Immune Defic Syndr (1999). 2021 https://doi.org/10.1097/qai.0000000000002687.

79.

Sarma MK, Pal A, Keller MA, Welikson T, Ventura J, Michalik DE, et al. White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling. Sci Rep. 2021;11(1):3086. https://doi.org/10.1038/s41598-021-82587-5.CrossRefPubMedPubMedCentral

80.

Wang P, Li J, Wang X, Thapa D, Wu GY. Asymptomatic human immunodeficiency virus vertical transmitted adolescents’ brain functional changes: based on resting-state functional magnetic resonance imaging. AIDS Res Hum Retrovir. 2018;34(8):699–704. https://doi.org/10.1089/aid.2017.0267.

81.

Heany SJ, Phillips N, Brooks S, Fouche JP, Myer L, Zar H, et al. Neural correlates of maintenance working memory, as well as relevant structural qualities, are associated with earlier antiretroviral treatment initiation in vertically transmitted HIV. J Neurovirol. 2020;26(1):60–9. https://doi.org/10.1007/s13365-019-00792-5.CrossRefPubMed

82.

Chiappini E, Bianconi M, Dalzini A, Petrara MR, Galli L, Giaquinto C, et al. Accelerated aging in perinatally HIV-infected children: clinical manifestations and pathogenetic mechanisms. Aging. 2018;10(11):3610–25. https://doi.org/10.18632/aging.101622.CrossRefPubMedPubMedCentral

83.

Malee KM, Smith RA, Mellins CA. Brain and cognitive development among U.S. youth with perinatally acquired human immunodeficiency virus infection. J Pediatr Infect Dis Soc. 2016;5(suppl 1):S1–s5 https://doi.org/10.1093/jpids/piw041.

84.

National Institutes of Health Office of AIDS Research. Reduce the incidence of HIV. https://www.oar.nih.gov/hiv-policy-and-research/research-priorities-overview/reduce-incidence-hiv. Accessed 17 Jan 2022.

85.

Vreeman RC, McCoy BM, Lee S. Mental health challenges among adolescents living with HIV. J Int AIDS Soc. 2017;20(Suppl 3):21497. https://doi.org/10.7448/ias.20.4.21497.CrossRefPubMedPubMedCentral

86.

Smith R, Huo Y, Tassiopoulos K, Rutstein R, Kapetanovic S, Mellins C, et al. Mental health diagnoses, symptoms, and service utilization in US youth with perinatal HIV infection or HIV exposure. AIDS Patient Care STDs. 2019;33(1):1–13. https://doi.org/10.1089/apc.2018.0096.CrossRefPubMed

87.

Abrams EJ, Mellins CA, Bucek A, Dolezal C, Raymond J, Wiznia A, et al. Behavioral health and adult milestones in young adults with perinatal HIV infection or exposure. Pediatrics. 2018;142(3) https://doi.org/10.1542/peds.2018-0938.

88.

Molinaro M, Adams HR, Mwanza-Kabaghe S, Mbewe EG, Kabundula PP, Mweemba M, et al. Evaluating the relationship between depression and cognitive function among children and adolescents with HIV in Zambia. AIDS Behav. 2021. https://doi.org/10.1007/s10461-021-03193-0.CrossRefPubMed

89.

Bucek A, Leu CS, Benson S, Warne P, Abrams EJ, Elkington KS, et al. Psychiatric disorders, antiretroviral medication adherence and viremia in a cohort of perinatally HIV-infected adolescents and young adults. Pediatr Infect Dis J. 2018;37(7):673–7. https://doi.org/10.1097/inf.0000000000001866.CrossRefPubMedPubMedCentral

90.

Boerwinkle AH, Meeker KL, Luckett P, Ances BM. Neuroimaging the neuropathogenesis of HIV. Curr HIV/AIDS Rep. 2021;18(3):221–8. https://doi.org/10.1007/s11904-021-00548-z.CrossRefPubMed

91.

Towe SL, Meade CS, Cloak CC, Bell RP, Baptiste J, Chang L. Reciprocal influences of HIV and cannabinoids on the brain and cognitive function. J Neuroimmune Pharmacol. 2020;15(4):765–79. https://doi.org/10.1007/s11481-020-09921-y.CrossRefPubMedPubMedCentral

92.

Saloner R, Fields JA, Marcondes MCG, Iudicello JE, von Känel S, Cherner M, et al. Methamphetamine and cannabis: a tale of two drugs and their effects on HIV, brain, and behavior. J Neuroimmune Pharmacol. 2020;15(4):743–64. https://doi.org/10.1007/s11481-020-09957-0.CrossRefPubMedPubMedCentral

93.

Lin Y, He JJ, Sorensen R, Chang L. Unraveling neuroHIV in the presence of substance use disorders. J Neuroimmune Pharmacol. 2020;15(4):578–83. https://doi.org/10.1007/s11481-020-09967-y.CrossRefPubMed

94.

Nickoloff-Bybel EA, Calderon TM, Gaskill PJ, Berman JW. HIV Neuropathogenesis in the presence of a disrupted dopamine system. J Neuroimmune Pharmacol. 2020;15(4):729–42. https://doi.org/10.1007/s11481-020-09927-6.CrossRefPubMedPubMedCentral

95.

Kallianpur KJ, Birn R, Ndhlovu LC, Souza SA, Mitchell B, Paul R, et al. Impact of cannabis use on brain structure and function in suppressed HIV infection. J Behav Brain Sci. 2020;10(8):344–70.CrossRefPubMedPubMedCentral

96.

Watson CW, Paolillo EW, Morgan EE, Umlauf A, Sundermann EE, Ellis RJ, et al. Cannabis exposure is associated with a lower likelihood of neurocognitive impairment in people living with HIV. J Acquir Immune Defic Syndr (1999). 2020;83(1):56–64 https://doi.org/10.1097/qai.0000000000002211.

97.

Hall SA, Lalee Z, Bell RP, Towe SL, Meade CS. Synergistic effects of HIV and marijuana use on functional brain network organization. Prog Neuro-Psychopharmacol Biol Psychiatry. 2021;104:110040. https://doi.org/10.1016/j.pnpbp.2020.110040.CrossRef

98.

Skalski LM, Towe SL, Sikkema KJ, Meade CS. Memory impairment in HIV-infected individuals with early and late initiation of regular marijuana use. AIDS Behav. 2018;22(5):1596–605. https://doi.org/10.1007/s10461-017-1898-z.CrossRefPubMedPubMedCentral

99.

Skalski LM, Towe SL, Sikkema KJ, Meade CS. The impact of marijuana use on memory in HIV-infected patients: a comprehensive review of the HIV and marijuana literatures. Curr Drug Abuse Rev. 2016;9(2):126–41. https://doi.org/10.2174/1874473709666160502124503.CrossRefPubMed

100.

Thames AD, Kuhn TP, Williamson TJ, Jones JD, Mahmood Z, Hammond A. Marijuana effects on changes in brain structure and cognitive function among HIV+ and HIV- adults. Drug Alcohol Depend. 2017;170:120–7. https://doi.org/10.1016/j.drugalcdep.2016.11.007.CrossRefPubMed

101.

Kapoor A, Tan CS. Immunotherapeutics to Treat HIV in the central nervous system. Curr HIV/AIDS Rep. 2020;17(5):499–506. https://doi.org/10.1007/s11904-020-00519-w.CrossRefPubMedPubMedCentral

102.

Chahroudi A, Wagner TA, Persaud D. CNS persistence of HIV-1 in children: the untapped reservoir. Curr HIV/AIDS Rep. 2018;15(5):382–7. https://doi.org/10.1007/s11904-018-0412-1.CrossRefPubMed

103.

Boivin MJ, Ruiseñor-Escudero H, Familiar-Lopez I. CNS impact of perinatal HIV infection and early treatment: the need for behavioral rehabilitative interventions along with medical treatment and care. Curr HIV/AIDS Rep. 2016;13(6):318–27. https://doi.org/10.1007/s11904-016-0342-8.CrossRefPubMedPubMedCentral

104.

Suter MK, Karr CJ, John-Stewart GC, Gómez LA, Moraa H, Nyatika D, et al. Implications of combined exposure to household air pollution and HIV on neurocognition in children. Int J Environ Res Public Health. 2018;15(1) https://doi.org/10.3390/ijerph15010163.

105.

Bather JR, Williams PL, Broadwell C, Smith R, Patel K, Garvie PA, et al. Racial/ethnic disparities in longitudinal emotional-behavioral functioning among youth born to women living with HIV. J Acquir Immune Defic Syndr. 2021;87(3):889–898 https://doi.org/10.1097/qai.0000000000002665.

106.

Nestadt DF, Saisaengjan C, McKay MM, Bunupuradah T, Pardo G, Lakhonpon S, et al. CHAMP+ Thailand: pilot randomized control trial of a family-based psychosocial intervention for perinatally HIV-infected early adolescents. AIDS Patient Care STDs. 2019;33(5):227–36. https://doi.org/10.1089/apc.2019.0021.CrossRefPubMedPubMedCentral

107.

Bhana A, Mellins CA, Small L, Nestadt DF, Leu CS, Petersen I, et al. Resilience in perinatal HIV+ adolescents in South Africa. AIDS Care. 2016;28 Suppl 2(sup2):49–59 https://doi.org/10.1080/09540121.2016.1176676.

108.

McKernan McKay M, Alicea S, Elwyn L, McClain ZR, Parker G, Small LA, et al. The development and implementation of theory-driven programs capable of addressing poverty-impacted children's health, mental health, and prevention needs: CHAMP and CHAMP+, evidence-informed, family-based interventions to address HIV risk and care. J Clin Child Adolesc Psychol 2014;43(3):428–441 https://doi.org/10.1080/15374416.2014.893519.

109.

Yadav-Samudrala BJ, Fitting S. Mini-review: The therapeutic role of cannabinoids in neuroHIV. Neurosci Lett. 2021;750:135717. https://doi.org/10.1016/j.neulet.2021.135717.CrossRefPubMedPubMedCentral

110.

Fraser S, Cockcroft K. Working with memory: computerized, adaptive working memory training for adolescents living with HIV. Child Neuropsychol. 2020;26(5):612–34. https://doi.org/10.1080/09297049.2019.1676407.CrossRefPubMed

111.

Pennar A, Naar S, Woods S, Nichols S, Outlaw A, Ellis D. Promoting resilience through neurocognitive functioning in youth living with HIV. AIDS Care. 2018;30(sup4):59–64. https://doi.org/10.1080/09540121.2019.1576851.CrossRefPubMed

112.

Woods SP, Doyle KL, Morgan EE, Naar-King S, Outlaw AY, Nichols SL, et al. Task importance affects event-based prospective memory performance in adults with HIV-associated neurocognitive disorders and HIV-infected young adults with problematic substance use. J Int Neuropsychol Soc. 2014;20(6):652–62. https://doi.org/10.1017/s1355617714000435.CrossRefPubMedPubMedCentral

113.

Chan T, Marta M, Hawkins C, Rackstraw S. Cognitive and neurologic rehabilitation strategies for central nervous system HIV infection. Curr HIV/AIDS Rep. 2020;17(5):514–21. https://doi.org/10.1007/s11904-020-00515-0.CrossRefPubMedPubMedCentral

114.

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(3):185–201. https://doi.org/10.1055/s-0038-1637020.CrossRefPubMedPubMedCentral

115.

Phillips NJ, Thomas KGF, Myer L, Sacktor N, Zar HJ, Stein DJ, et al. Screening for HIV-associated neurocognitive disorders in perinatally infected adolescents: youth-International HIV Dementia Scale validation. AIDS (London, England). 2019;33(5):815–24. https://doi.org/10.1097/qad.0000000000002144.CrossRef

116.

Robbins RN, Kluisza L, Liu J, Santoro AF, Raymond J, Ngyuen N, et al. Construct validity supports use of a novel, tablet-based neurocognitive assessment for adolescents and young adults affected by perinatal HIV from vulnerable communities in the United States. AIDS Behav. 2020. https://doi.org/10.1007/s10461-020-03099-3.CrossRefPubMedPubMedCentral

117.

Scott JC, Van Pelt AE, Port AM, Njokweni L, Gur RC, Moore TM, et al. Development of a computerised neurocognitive battery for children and adolescents with HIV in Botswana: study design and protocol for the Ntemoga study. BMJ Open. 2020;10(8):e041099. https://doi.org/10.1136/bmjopen-2020-041099.CrossRefPubMedPubMedCentral

118.

Paul RH, Cho KS, Belden AC, Mellins CA, Malee KM, Robbins RN, et al. Machine-learning classification of neurocognitive performance in children with perinatal HIV initiating de novo antiretroviral therapy. AIDS (London, England). 2020;34(5):737–48. https://doi.org/10.1097/qad.0000000000002471.CrossRef

119.

Hoare J, Phillips N, Joska JA, Paul R, Donald KA, Stein DJ, et al. Applying the HIV-associated neurocognitive disorder diagnostic criteria to HIV-infected youth. Neurology. 2016;87(1):86–93. https://doi.org/10.1212/wnl.0000000000002669.CrossRefPubMedPubMedCentral

120.

Sanislow CA, Ferrante M, Pacheco J, Rudorfer MV, Morris SE. Advancing translational research using NIMH research domain criteria and computational methods. Neuron. 2019;101(5):779–82. https://doi.org/10.1016/j.neuron.2019.02.024.CrossRefPubMed

Title: Central Nervous System Impact of Perinatally Acquired HIV in Adolescents and Adults: an Update
Author: Sharon L. Nichols
Publication date: 01-02-2022
Publisher: Springer US
Keyword: Human Immunodeficiency Virus
Published in: Current HIV/AIDS Reports / Issue 1/2022
Print ISSN: 1548-3568
Electronic ISSN: 1548-3576
DOI: https://doi.org/10.1007/s11904-021-00598-3

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Central Nervous System Impact of Perinatally Acquired HIV in Adolescents and Adults: an Update

Abstract

Purpose of Review

Recent Findings

Summary

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 1/2022

Intersecting Pandemics of HIV and SARS-CoV-2: Commentary on the Special Issue

HIV and COVID-19 in Latin America and the Caribbean

HIV and SARS-CoV-2 Co-infection: Epidemiological, Clinical Features, and Future Implications for Clinical Care and Public Health for People Living with HIV (PLWH) and HIV Most-at-Risk Groups

Social and Behavioral Impacts of COVID-19 on People Living with HIV: Review of the First Year of Research

Impact of Chronic HIV Infection on SARS-CoV-2 Infection, COVID-19 Disease and Vaccines

Adventures in COVID-19 Policy Modeling: Education Edition

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page