Background
Healthy individuals who contract SARS-CoV-2 exhibit structural brain changes after infection. To assess whether SARS-CoV-2 is associated with unique or additive brain effects among people with HIV (PWH), we capitalized on systematic longitudinal 3T MRIs captured in the RV254 acute HIV (AHI) Thai cohort to compare changes between PWH who did or did not acquire SARS-CoV-2 infection.
Methods
RV254 participants are enrolled and offered antiretroviral therapy (ART) during AHI. This analysis included PWH who underwent longitudinal 3T MRI, with the first scan acquired ≥5 months after ART initiation. Participants who then acquired SARS-CoV-2 (COVID+ PWH) between 2 scans were compared to those who completed >2 scans prior to 2020 and thus were SARS-CoV-2 naïve (COVID- PWH). Selected regions included those susceptible to SARS-CoV-2 (olfactory cortex, superior frontal gyrus, orbital gyrus, gyrus rectus, hippocampus, and amygdala), and HIV (caudate, pallidum, putamen, thalamus, nucleus accumbens). Volumes were summed across hemispheres and corrected for head size. Longitudinal differences were assessed using a repeated-measures MANOVA with a false discovery rate (FDR) correction for multiple comparisons.
Results
Fifty RV254 COVID+ PWH (pre-COVID scan at median=5.6 years after ART initiation) were compared to 16 COVID- PWH. Subgroups did not differ by age, CD4 count, or HIV RNA detection rate (overall median [IQR] baseline 27 [23-31] years, 632 [476-859] CD4+ cells/µL, 1.5% detectable); baseline CD4/CD8 ratio was lower in COVID+ PWH (p=.031). Volumetric trajectories differed significantly by group in the superior frontal (p<.001), anterior orbital (p=.014), and medial orbitofrontal (p=.043) gyri, and nucleus accumbens (p=.037). Only the change between groups in the superior frontal gyrus remained significant after FDR correction (p=.002), where COVID+ PWH had volumetric decreases (-339 mm3) while COVID- PWH exhibited increases (+393 mm3).
Conclusions
In the longitudinal RV254 study, participants acquiring SARS-CoV-2 demonstrated evidence of structural brain changes over time compared to those followed prior to the COVID pandemic in regions susceptible to both conditions despite well-controlled HIV viremia. This implicates frontal gray matter in as a potential locus of SARS-CoV-2 impacts among PWH. Additional work will more fully evaluate temporal profiles and mechanisms of brain change relative to both conditions independently as well as their potential synergistic effect on brain integrity.
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