title: Multivariable analysis to determine if HIV-1 Tat dicysteine motif is associated with neurodevelopmental delay in HIV-infected children in Malawi.
abstract: BACKGROUND
  HIV-1 Tat protein is implicated in HIV-neuropathogenesis. Tat C31S polymorphism (Tat(CS)) 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 Tat(CS) 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 Tat(CC) was 27 %. Z-scores for BSID-III subtests ranged from -1.3 to -3.9. Tat(CC) was not associated with higher BSID-III z-scores.
  
  
  CONCLUSIONS
  The hypothesis of milder neuropathology in individuals infected with HIV Tat(CS) 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.
authors.affiliation: Department of Pediatrics, Montefiore Medical Center, Bronx, NY, USA. jdara@montefiore.org.
authors.forename: Jasmeen
authors.initials: J
authors.lastname: Dara
authors.affiliation: UNC School of Public Health, University of North Carolina, Chapel Hill, NC, USA. adow@email.unc.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Dow
authors.affiliation: UNC School of Public Health, University of North Carolina, Chapel Hill, NC, USA. ecromwe@live.unc.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cromwell
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA. christa_buckheit@med.unc.edu.
authors.forename: Christa Buckheit
authors.initials: CB
authors.lastname: Sturdevant
authors.affiliation: Malawi-Liverpool Wellcome Trust and Department of Pediatrics, College of Medicine, Blantyre, Malawi. macphers@liverpool.ac.uk.
authors.forename: Macpherson
authors.initials: M
authors.lastname: Mallewa
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA. ron_swanstrom@med.unc.edu.
authors.forename: Ronald
authors.initials: R
authors.lastname: Swanstrom
authors.affiliation: UNC School of Public Health, University of North Carolina, Chapel Hill, NC, USA. vanrie@email.unc.edu.
authors.forename: Annelies
authors.initials: A
authors.lastname: Van Rie
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA. vinayaka.prasad@einstein.yu.edu.
authors.forename: Vinayaka R
authors.initials: VR
authors.lastname: Prasad
mesh_terms: D020816:Amino Acid Motifs; D003430:Cross-Sectional Studies; D002658:Developmental Disabilities / Q000821:virology*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000523:psychology* / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007223:Infant; D008295:Malawi; D008297:Male; D019562:Viral Load; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D054322:tat Gene Products, Human Immunodeficiency Virus