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

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.