Auditory white matter tract development in infants exposed to HIV and antiretrovirals

Although HIV exposure has previously been found to affect brain white matter (WM) tract integrity and language development in infants and children, the impacts of HIV and antiretroviral therapy (ART) exposure on central auditory tracts remain unclear. Moreover, no research to date has investigated the relationship between auditory WM tract development and language outcomes in infants exposed to HIV but uninfected (iHEU). Brain images were acquired at the age of 0-5 weeks for 31 infants whose mothers began ART pre-conception (iHEU-pre), 29 infants whose mothers began ART post-conception (iHEU-post) and 25 infants who were HIV-unexposed (iHU). Full-probabilistic diffusion tensor imaging (DTI) tractography was used to assess WM integrity in tracts connected to central auditory structures. Language assessments were carried out at 9-14 months using the Griffiths Mental Development Scales (GMDS). Linear regression analysis was used to compare DTI tractography results between iHEU and iHU and to assess the relationship between DTI measures and language. Finally, the impacts of HIV and ART exposure on associations between language and DTI measures were visualised using groupwise language-DTI correlation plots. There were no results after multiple comparison correction. Unadjusted results show recurring patterns of reduced fractional anisotropy (FA), driven by iHEU-post, in auditory tracts of iHEU compared to iHU. Both iHEU-pre and iHEU-post contributed to the patterns of uncorrected elevations in mean diffusivity (MD) observed in the entire iHEU group, with the left medial geniculate nucleus being the auditory structure most frequently observed within the affected tracts. Effect sizes of uncorrected differences, which were small-to-moderate in size, were similar to other infant DTI tractography studies. Groupwise assessment of the data revealed moderately strong correlations between GMDS language scores and DTI measures in some affected tracts, only for iHU. Our findings indicate that HIV/ART exposure may have subtle effects on auditory WM tract development in infants. Delays in auditory tract maturation appear to occur irrespective of ART exposure duration and may be HIV exposure-specific effects. Tracts connected to the left auditory thalamus have notably been implicated in our unadjusted results. HIV and ART exposure may interfere with the way in which auditory WM tracts mature, potentially impacting the role of a small number of these tracts in language processing.