Skip to main content Accessibility help

Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda

  • H. Ruiseñor-Escudero (a1), I. Familiar (a1), N. Nakasujja (a2), P. Bangirana (a2), R. Opoka (a2), B. Giordani (a3) and M. Boivin (a1)...

HIV can affect the neuropsychological function of children, including their behavior. We aim to identify immunological correlates of behavioral problems among children living with HIV in Uganda.


Children participating in a parent randomized control trial in Kayunga, Uganda were assessed with the Behavior Rating Inventory of Executive Function (BRIEF) and the Child Behavior Checklist (CBCL). We constructed simple and multiple linear regression models to identify immunological correlates of behavioral problems.


A total of 144 children living with HIV (50% male) with a mean age of 8.9 years [Standard Deviation (s.d.) = 1.9] were included in the analysis. Eighty-two children were on antiretroviral therapy. Mean CD4 cell count % was 35.1 cells/μl (s.d. = 15.0), mean CD4 cell activation 5.7% (s.d. = 5.1), mean CD8 cell activation was 17.5% (s.d. = 11.2) and 60 children (41.7%) had a viral load of <4000 copies/ml. In the adjusted models for the BRIEF, higher scores were associated with higher viral loads (aβ = 16.7 × 10−6, 95% CI −5.00 × 10−6 to 28.4 × 10−6), specifically on the behavioral regulation index. Higher mean CD8 activation % was associated with higher scores on the Externalizing Problems  and Total Problems  scales of the CBCL (aβ = 0.17, 95% CI 0.04–0.31 and aβ = 0.15, 95% CI 0.00–0.28, respectively).


Poorer behavioral outcomes were associated with higher viral loads while higher CD8 activation was associated with poorer emotional and behavioral outcomes. Complete immunological assessments for children living with HIV could include commonly used viral and immunological parameters to identify those at higher risk of having negative behavior outcomes and who would benefit the most from behavioral interventions.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda
      Available formats
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
* Address for correspondence: H. Ruiseñor-Escudero, Department of Psychiatry, East Lansing, Michigan State University, Michigan, USA. (Email:
Hide All
Achenbach, TM (1991). Integrative Guide to the 1991 CBCL/4-18, YSR, and TRF Profiles. Burlington, VT: University of Vermont, Department of Psychology.
Appay, V, Sauce, D (2008). Immune activation and inflammation in HIV-1 infection: causes and consequences. Journal of Pathology 214, 231241.
Bangirana, P, Nakasujja, N, Giordani, B, Opoka, R, John, C, Boivin, M (2009 a). Psychometric properties of the Luganda version of the Child Behaviour Checklist in Ugandan children. Child and Adolescent Psychiatry and Mental Health 3, 38.
Bangirana, P, Nakasujja, N, Giordani, B, Opoka, RO, John, CC, Boivin, MJ (2009 b). Reliability of the Luganda version of the Child Behaviour Checklist in measuring behavioural problems after cerebral malaria. Child Adolescent Psychiatry and Mental Health 3, 38. doi: 10.1186/1753-2000-3-38.
Bisiacchi, PS, Suppiej, A, Laverda, A (2000). Neuropsychological evaluation of neurologically asymptomatic HIV-infected children. Brain and Cognition 43, 4952.
Black, MM, Baqui, AH, Zaman, K, McNary, SW, Le, K, Arifeen, SE, Black, RE (2007). Depressive symptoms among rural Bangladeshi mothers: implications for infant development. Journal of Child Psychology and Psychiatry 48, 764772. doi:10.1111/j.1469-7610.2007.01752.x.
Boivin, MJ, Bangirana, P, Nakasujja, N, Page, CF, Shohet, C, Givon, D, Klein, PS (2013). A year-long caregiver training program improves cognition in preschool Ugandan children with human immunodeficiency virus. Journal of Pediatrics 163, 14091416. e1401–e1405. doi:10.1016/j.jpeds.2013.06.055.
Boivin, MJ, Green, SD, Davies, AG, Giordani, B, Mokili, JK, Cutting, WA (1995). A preliminary evaluation of the cognitive and motor effects of pediatric HIV infection in Zairian children. Health Psychology 14, 1321.
Boivin, MJ, Ruel, TD, Boal, HE, Bangirana, P, Cao, H, Eller, LA, Wong, JK (2010). HIV-subtype A is associated with poorer neuropsychological performance compared with subtype D in antiretroviral therapy-naive Ugandan children. AIDS 24, 11631170.
Bomba, M, Nacinovich, R, Oggiano, S, Cassani, M, Baushi, L, Bertulli, C, Badolato, R (2010). Poor health-related quality of life and abnormal psychosocial adjustment in Italian children with perinatal HIV infection receiving highly active antiretroviral treatment. AIDS Care 22, 858865. doi:10.1080/09540120903483018.
Drotar, D, Olness, K, Wiznitzer, M, Guay, L, Marum, L, Svilar, G, Kiziri-Mayengo, R (1997). Neurodevelopmental outcomes of Ugandan infants with human immunodeficiency virus type 1 infection. Pediatrics 100, E5.
Gadow, KD, Angelidou, K, Chernoff, M, Williams, PL, Heston, J, Hodge, J, Nachman, S (2012). Longitudinal study of emerging mental health concerns in youth perinatally infected with HIV and peer comparisons. Journal of Developmental and Behavioral Pediatrics 33, 456468. doi:10.1097/DBP.0b013e31825b8482.
Ghafouri, M, Amini, S, Khalili, K, Sawaya, BE (2006). HIV-1 associated dementia: symptoms and causes. Retrovirology 3, 28.
Gioia, GA, Isquith, PK, Guy, SC, Kenworthy, L (2000). Test review behavior rating inventory of executive function. Child Neuropsychology 6, 235238.
Händel, M, Artelt, C, Weinert, S (2013). Assessing metacognitive knowledge: development and evaluation of a test instrument. Journal for Educational Research Online/Journal für Bildungsforschung Online 5, 162188.
Jennings, C, Rich, K, Siegel, JN, Landay, A (1994). A phenotypic study of CD8+ lymphocyte subsets in infants using three-color flow cytometry. Clinical Immunology and Immunopathology 71, 813.
Jeremy, RJ, Kim, S, Nozyce, M, Nachman, S, McIntosh, K, Pelton, SI, Stanley, K (2005). Neuropsychological functioning and viral load in stable antiretroviral therapy-experienced HIV-infected children. Pediatrics 115, 380387. doi: 10.1542/peds.2004-1108.
Joint United Nations Program on HIV/AIDS, U. (2015). Uganda: HIV and AIDS estimates (2013). Retrieved February 2015, 2015, from
Kapetanovic, S, Aaron, L, Montepiedra, G, Burchett, SK, Kovacs, A (2012). T-cell activation and neurodevelopmental outcomes in perinatally HIV-infected children. Aids 26, 959969. doi:10.1097/QAD.0b013e328352cee7.
Keiley, MK, Bates, JE, Dodge, KA, Pettit, GS (2000). A cross-domain growth analysis: externalizing and internalizing behaviors during 8 years of childhood. Journal of Abnormal Child Psychology 28, 161179.
Kovacs, A (2009). Early immune activation predicts central nervous system disease in HIV-infected infants: Implications for early treatment. Clinical Infectious Diseases 48, 347349.
Laughton, B, Cornell, M, Boivin, M, Van Rie, A (2013). Neurodevelopment in perinatally HIV-infected children: a concern for adolescence. Journal of the International AIDS Society 16, 18603. doi:10.7448/ias.16.1.18603.
Levenson, RL Jr., Mellins, CA, Zawadzki, R, Kairam, R, Stein, Z (1992). Cognitive assessment of human immunodeficiency virus-exposed children. American Journal of Diseases of Children 146, 14791483.
Llorente, AM, Brouwers, P, Leighty, R, Malee, K, Smith, R, Harris, L, Chase, C (2014). An analysis of select emerging executive skills in perinatally HIV-1-infected children. Applied Neuropsychology–Child 3, 1025. doi: 10.1080/21622965.2012.686853.
Marcotte, TD, Deutsch, R, McCutchan, JA, Moore, DJ, Letendre, S, Ellis, RJ, Grant, I (2003). Prediction of incident neurocognitive impairment by plasma HIV RNA and CD4 levels early after HIV seroconversion. Archives of Neurology 60, 14061412. doi: 10.1001/archneur.60.10.1406.
McCloskey, TW, Kohn, N, Lesser, M, Bakshi, S, Pahwa, S (2001). Immunophenotypic analysis of HIV-infected children: alterations within the first year of life, changes with disease progression, and longitudinal analyses of lymphocyte subsets. Cytometry 46, 157165.
Mekmullica, J, Brouwers, P, Charurat, M, Paul, M, Shearer, W, Mendez, H, Smith, R (2009). Early immunological predictors of neurodevelopmental outcomes in HIV-infected children. Clinical Infectious Diseases 48, 338346.
Mellins, CA, Elkington, KS, Leu, CS, Santamaria, EK, Dolezal, C, Wiznia, A, Abrams, EJ (2012). Prevalence and change in psychiatric disorders among perinatally HIV-infected and HIV-exposed youth. AIDS Care 24, 953962. doi:10.1080/09540121.2012.668174.
Mellins, CA, Kang, E, Leu, CS, Havens, JF, Chesney, MA (2003). Longitudinal study of mental health and psychosocial predictors of medical treatment adherence in mothers living with HIV disease. AIDS Patient Care and STDs 17, 407416. doi: 10.1089/108729103322277420.
Mellins, CA, Malee, KM (2013). Understanding the mental health of youth living with perinatal HIV infection: lessons learned and current challenges. Journal of the International AIDS Society 16, 18593. doi: 10.7448/ias.16.1.18593.
Mellins, CA, Smith, R, O'Driscoll, P, Magder, LS, Brouwers, P, Chase, C, Matzen, E (2003). High rates of behavioral problems in perinatally HIV-infected children are not linked to HIV disease. Pediatrics 111, 384393.
Naar-King, S, Montepiedra, G, Garvie, P, Kammerer, B, Malee, K, Sirois, PA, Nichols, SL (2013). Social ecological predictors of longitudinal HIV treatment adherence in youth with perinatally acquired HIV. Journal of Pediatric Psychology 38, 664674. doi:10.1093/jpepsy/jst017.
Nachman, S, Chernoff, M, Williams, P, Hodge, J, Heston, J, Gadow, KD (2012). Human immunodeficiency virus disease severity, psychiatric symptoms, and functional outcomes in perinatally infected youth. Archives of Pediatrics and Adolescent Medicine 166, 528535.
Rescorla, LA, Achenbach, TM, Ginzburg, S, Ivanova, M, Dumenci, L, Almqvist, F, Domuta, A (2007). Consistency of teacher-reported problems for students in 21 countries. School Psychology Review 36, 91110.
Sacktor, N, Nakasujja, N, Skolasky, RL, Rezapour, M, Robertson, K, Musisi, S, Quinn, TC (2009). HIV subtype D is associated with dementia, compared with subtype A, in immunosuppressed individuals at risk of cognitive impairment in Kampala, Uganda. Clinical Infectious Diseases 49, 780786. doi: 10.1086/605284.
Sanchez-Ramon, S, Bellon, JM, Resino, S, Canto-Nogues, C, Gurbindo, D, Ramos, JT, Munoz-Fernandez, MA (2003). Low blood CD8+ T-lymphocytes and high circulating monocytes are predictors of HIV-1-associated progressive encephalopathy in children. Pediatrics 111, E168E175.
Shala, M, Dhamo, M (2013). Prevalence of behavioural and emotional problems among two to five years old Kosovar preschool children—Parent's Report. Psychology 4, 1008.
Tadesse, AW, Berhane Tsehay, Y, Girma Belaineh, B, Alemu, YB (2012). Behavioral and emotional problems among children aged 6–14 years on highly active antiretroviral therapy in Addis Ababa: a cross-sectional study. AIDS Care 24, 13591367. doi: 10.1080/09540121.2011.650677.
Tobin, NH, Aldrovandi, GM (2013). Immunology of pediatric HIV infection. Immunological Reviews 254, 143169.
Ultmann, MH, Diamond, GW, Ruff, HA, Belman, AL, Novick, BE, Rubinstein, A, Cohen, HJ (1987). Developmental abnormalities in children with acquired immunodeficiency syndrome (AIDS): a follow-up study. International Journal of Neuroscience 32, 661667.
UNAIDS. (2013). Uganda Country Progress Report.
Wachsler-Felder, JL, Golden, CJ (2002). Neuropsychological consequences of HIV in children: a review of current literature. Clinical Psychology Review 22, 443464.
Wolters, PL, Brouwers, P (2005). Neurobehavioral function and assessment of children and adolescents with HIV-1 infection. Textbook for Pediatric Care, Part II, Chapter 17, pp. 269284.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Global Mental Health
  • ISSN: -
  • EISSN: 2054-4251
  • URL: /core/journals/global-mental-health
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed