Multivariable analysis to determine if HIV-1 Tat dicysteine motif is associated with neurodevelopmental delay in HIV-infected children in Malawi

Jasmeen Dara, Anna Dow, Elizabeth Cromwell, Christa Buckheit Sturdevant, Macpherson Mallewa, Ronald Swanstrom, Annelies Van Rie, Vinayaka R. Prasad

Research output: Contribution to journalArticlepeer-review

Abstract

Background: HIV-1 Tat protein is implicated in HIV-neuropathogenesis. Tat C31S polymorphism (TatCS) has been associated with milder neuropathology in vitro and in animal models but this has not been addressed in a cohort of HIV-infected adults or children. Methods: HIV viral load (VL) in plasma and cerebrospinal fluid (CSF) were determined and plasma HIV tat gene was sequenced. Neurodevelopmental assessment was performed using Bayley Scales of Infant Development III (BSID-III), with scores standardized to Malawian norms. The association between TatCS and BSID-III scores was evaluated using multivariate linear regression. Results: Neurodevelopmental assessment and HIV tat genotyping were available for 33 children. Mean age was 19.4 (SD 7.1) months, mean log VL was 5.9 copies/mL (SD 0.1) in plasma and 3.9 copies/mL (SD 0.9) in CSF. The prevalence of TatCC was 27 %. Z-scores for BSID-III subtests ranged from - 1.3 to - 3.9. TatCC was not associated with higher BSID-III z-scores. Conclusions: The hypothesis of milder neuropathology in individuals infected with HIV TatCS was not confirmed in this small cohort of Malawian children. Future studies of tat genotype and neurocognitive disorder should be performed using larger sample sizes and investigate if this finding is due to differences in HIV neuropathogenesis between children and adults.

Original languageEnglish (US)
Article number38
JournalBehavioral and Brain Functions
Volume11
Issue number1
DOIs
StatePublished - Dec 17 2015

Keywords

  • Dicysteine motif
  • Encephalopathy
  • HIV-1
  • HIV-1 subtype C
  • Neurodevelopment
  • Tat

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Biological Psychiatry
  • Behavioral Neuroscience

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