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

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Creator
  • Mallewa, Macpherson
    • Other Affiliation: Malawi‑Liverpool Wellcome Trust and Department of Pediatrics, College of Medicine, Blantyre, Malawi
  • Dow, Anna
    • Affiliation: Gillings School of Global Public Health
  • Cromwell, Elizabeth
    • Affiliation: Gillings School of Global Public Health
  • Dara, Jasmeen
    • Other Affiliation: Department of Pediatrics, Montefiore Medical Center, Bronx, NY, USA
  • Swanstrom, Ronald
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
  • Sturdevant, Christa B
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
  • Prasad, Vinayaka R
    • Other Affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
  • Van Rie, Annelies
    • Affiliation: Gillings School of Global Public Health
Abstract
  • 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.
Date of publication
Identifier
  • doi:10.1186/s12993-015-0083-7
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Dara et al.
Language
  • English
Bibliographic citation
  • Behavioral and Brain Functions. 2015 Dec 17;11(1):38
Publisher
  • BioMed Central
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