A Pilot Investigation of the Association Between Vpr Amino Acid Substitutions and Peripheral Immune Marker Levels in People With Human Immunodeficiency Virus: Implications for Neurocognitive Impairment

Abstract

Background Subtype-specific amino acid variations in viral proteins of HIV-1 influence disease progression. Furthermore, Vpr sequence variation correlates with chronic inflammation, a central mechanism in HIV-1 (neuro)pathogenesis. Nevertheless, no clinical study has investigated the link between Vpr sequence variation and peripheral inflammation in people living with HIV. The aim of this pilot study was to ascertain whether specific Vpr amino acid variants were associated with immune markers in people living with HIV. Methods We included a unique cohort of forty-eight treatment-naïve South African people living with HIV to determine the association between blood-derived Vpr sequence variation and peripheral immune marker levels using Sanger sequencing and ELISA analysis, respectively. Results Our findings indicate that among the many neuropathogenic Vpr amino acid variants and immune markers examined, after applying Bonferroni corrections (p = .05/3) and adjusting for sex and locality, suPAR was nearing significance for higher levels in participants with the G41 amino acid variant compared to those with the S41 variant (p = .035), after. Further, amino acid variations at position 41 (between G41 and S41) exhibited a significant association with suPAR (adj R2 = .089, β = .386; 95% CI .125 to 3.251; p = .035). Conclusions These findings suggest that Vpr amino acid sequence variations might contribute to dysregulated inflammation, which could explain the observed association between specific Vpr variants and HIV-1 (neuro)pathogenesis found in prior research. These Vpr variants merit further investigation to fully understand their roles in HIV-1 pathogenesis and neuropathogenesis.