Retrospective Observational Study of CSF-Derived HIV-1 Tat and Vpr Amino Acid Sequences in a South African Pediatric Cohort with HIV Subtype C

The human immunodeficiency virus (HIV-1) infiltrates the central nervous system (CNS) early in infection, leading to HIV-associated neurocognitive impairments, particularly pronounced in children who exhibit neurodevelopmental delay. Viral proteins, including the transactivator of transcription protein (Tat) and viral protein R (Vpr) are pivotal in HIV-1 neuropathogenesis, with their amino acid sequence variation influencing disease progression. Due to the difficulty of collecting cerebrospinal fluid from children, few studies have examined whether key Tat and Vpr neuropathogenic signatures found in blood are also present in the cerebrospinal fluid (CSF) of children with HIV. We employed Sanger sequencing for Tat and Vpr sequence analysis using retrospectively collected CSF samples from a South African pediatric HIV-1 subtype C cohort (n = 4). We compared our CSF-derived sequences with pediatric blood-derived sequences (n = 43) from various geographical regions, sourced from the Los Alamos database. Neuropathogenic amino acid variants were identified in Tat and Vpr sequences derived from CSF samples of South African pediatric participants No significant differences were found between subtype C sequences from CSF and blood. Regional analysis highlighted unique amino acid signatures. Obtaining pediatric CSF for HIV-1 sequencing is highly challenging. Despite a small sample size, this study offers rare insights into Tat and Vpr sequences in children, improving understanding of the potential HIV-1 brain pathogenesis in pediatric populations.