Viral heritability of neurocognitive performances in persons living with HIV and underlying viral residue variants

Neurocognitive impairments (NCI) affect up to 50% of persons living with HIV (PLWH), even under anti-retroviral therapy. Evidence suggests that HIV-1 genotypes at least in part contribute to NCI, but most studies considered composite scores and did not examine specific neurocognitive domains. We considered neurocognitive domains assessed in the Neurocognitive Assessment in the Metabolic and Ageing Cohort, a sub study of the Swiss HIV Cohort Study (SHCS), and determined associations with HIV-1 residues, detected by full-length genome sequencing, previously linked to self-reported neurocognitive complaints (SRNC) in the SHCS, using linear regression. Additionally, we determined the heritability with Brownian motion- and mixed models based on viral pol phylogenies. In 192 out of 981 PLWH with full-length sequences, among the top residue variants identified, Env641E and Rev18I had been previously associated with SRNC. Respectively, of identified residue variants, point estimates correlated highly with previous SRNC-estimates from the SHCS for sensory skills (r = -0.71, P < 0.0001) and speed of processing (r = -0.71, P < 0.0001). Heritability estimates in 981 PLWH were significant for sensory skills [25.9%, 95% confidence interval (CI) 5.5-44.6%], motor skills (24.3%, CI 3.7-43.3%), and speed of processing (23.5%, CI 5.2-40.7%). Our findings support prior observations regarding SRNC-associated viral residues and confirm the relevance of the infecting HIV-1 strains for neurocognitive performances.