Skip to main content

Vitamin D is not associated with HIV-associated neurocognitive disorder in Rakai, Uganda


We investigated whether vitamin D is associated with HIV-associated neurocognitive disorder (HAND). HIV-infected (HIV+) antiretroviral therapy (ART)-naïve adults in rural Uganda underwent a neurocognitive battery for determination of HAND stage at baseline and after 2 years. Baseline serum 25-hydroxyvitamin D (25OH-D) and serum and cerebrospinal fluids (CSF) vitamin D-binding protein (VDBP) were obtained. Of the 399 participants, 4% (n = 16) were vitamin D deficient (25OH-D < 20 ng/mL). There was no association between 25OH-D, serum or CSF VDBP, and HAND stage at baseline or follow-up. Future studies in a population with higher levels of vitamin D deficiency may be warranted.

This is a preview of subscription content, access via your institution.


  • Anthony IC, Norrby KE, Dingwall T, Carnie FW, Millar T, Arango JC, Robertson R, Bell JE (2010) Predisposition to accelerated Alzheimer-related changes in the brains of human immunodeficiency virus negative opiate abusers. Brain 133:3685–3698

    Article  PubMed  Google Scholar 

  • Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799

    Article  CAS  PubMed  Google Scholar 

  • Berridge MJ (2014) Calcium regulation of neural rhythms, memory and Alzheimer’s disease. J Physiol 592:281–293

    Article  CAS  PubMed  Google Scholar 

  • Bishnoi RJ, Palmer RF, Royall DR (2015) Vitamin D binding protein as a serum biomarker of Alzheimer’s disease. J Alzheimers Dis 43:37–45

    Article  CAS  PubMed  Google Scholar 

  • Clifford DB, Fagan AM, Holtzman DM, Morris JC, Teshome M, Shah AR, Kauwe JS (2009) CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology 73:1982–1987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ezeamama AE, Guwatudde D, Wang M, Bagenda D, Kyeyune R, Sudfeld C, Manabe YC, Fawzi WW (2015) 'Vitamin-D deficiency impairs CD4+T-cell count recovery rate in HIV-positive adults on highly active antiretroviral therapy: a longitudinal study. Clin Nutr

  • Giunta B, Ehrhart J, Obregon DF, Lam L, Le L, Jin J, Fernandez F, Tan J, Shytle RD (2011) Antiretroviral medications disrupt microglial phagocytosis of beta-amyloid and increase its production by neurons: implications for HIV-associated neurocognitive disorders. Mol Brain 4:23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johansson P, Almqvist EG, Johansson JO, Mattsson N, Andreasson U, Hansson O, Wallin A, Blennow K, Zetterberg H, Svensson J (2013) Cerebrospinal fluid (CSF) 25-hydroxyvitamin D concentration and CSF acetylcholinesterase activity are reduced in patients with Alzheimer’s disease. PLoS One 8:e81989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klassen KM, Fairley CK, Chen M, Kimlin MG, Karahalios A, Ebeling PR (2015) Vitamin D deficiency may be associated with a more rapid decline in CD4 cell count to <350 cells/muL in untreated HIV-infected adults. Curr HIV Res

  • Krut JJ, Zetterberg H, Blennow K, Cinque P, Hagberg L, Price RW, Studahl M, Gisslen M (2013) Cerebrospinal fluid Alzheimer’s biomarker profiles in CNS infections. J Neurol 260:620–626

    Article  CAS  PubMed  Google Scholar 

  • Mehta S, Giovannucci E, Mugusi FM, Spiegelman D, Aboud S, Hertzmark E, Msamanga GI, Hunter D, Fawzi WW (2010) Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality. PLoS One 5:e8770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moon M, Song H, Hong HJ, Nam DW, Cha MY, Oh MS, Yu J, Ryu H, Mook-Jung I (2013) Vitamin D-binding protein interacts with Abeta and suppresses Abeta-mediated pathology. Cell Death Differ 20:630–638

    Article  CAS  PubMed  Google Scholar 

  • Morley JE, Farr SA (2014) The role of amyloid-beta in the regulation of memory. Biochem Pharmacol 88:479–485

    Article  CAS  PubMed  Google Scholar 

  • Muenchhoff J, Poljak A, Song F, Raftery M, Brodaty H, Duncan M, McEvoy M, Attia J, Schofield PW, Sachdev PS (2015) Plasma protein profiling of mild cognitive impairment and Alzheimer’s disease across two independent cohorts. J Alzheimers Dis 43:1355–1373

    Article  CAS  PubMed  Google Scholar 

  • Ortega M, Ances BM (2014) Role of HIV in amyloid metabolism. J NeuroImmune Pharmacol 9:483–491

    Article  PubMed  PubMed Central  Google Scholar 

  • Rempel HC, Pulliam L (2005) HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS 19:127–135

    Article  CAS  PubMed  Google Scholar 

  • Rozek W, Ricardo-Dukelow M, Holloway S, Gendelman HE, Wojna V, Melendez LM, Ciborowski P (2007) Cerebrospinal fluid proteomic profiling of HIV-1-infected patients with cognitive impairment. J Proteome Res 6:4189–4199

    Article  CAS  PubMed  Google Scholar 

  • Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M, Mankowski JL, Brown A, Volsky DJ, McArthur JC (2016) HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat Rev Neurol 12:234–248

    Article  PubMed  PubMed Central  Google Scholar 

  • Sudfeld CR, Wang M, Aboud S, Giovannucci EL, Mugusi FM, Fawzi WW (2012) Vitamin D and HIV progression among Tanzanian adults initiating antiretroviral therapy. PLoS One 7:e40036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeshokumar AK, Saylor D, Kornberg MD, Mowry EM (2015) Evidence for the importance of vitamin D status in neurologic conditions. Curr Treat Options Neurol 17:51

    Article  PubMed  Google Scholar 

Download references


The authors would like to thank the study participants and staff at the Rakai Health Sciences Program for the time and effort they dedicated to this study.


This study is supported by the National Institutes of Health (MH099733, MH075673, MH080661-08, L30NS088658, NS065729-05S2, P30AI094189-01A1) and the Johns Hopkins Center for Global Health.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Deanna Saylor.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Saylor, D., Nakigozi, G., Pardo, C.A. et al. Vitamin D is not associated with HIV-associated neurocognitive disorder in Rakai, Uganda. J. Neurovirol. 25, 410–414 (2019).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • HIV-associated neurocognitive disorder
  • Vitamin D
  • HIV
  • Africa
  • Epidemiology