Coreceptor usage of plasma and cerebrospinal fluid-derived HIV-1 subtype C variants

Abstract

Our findings reveal compartment-specific heterogeneity in HIV-1 subtype C coreceptor usage during advanced infection. CSF-derived variants were primarily limited to CCR5 usage, while plasma-derived variants exhibited broader usage of CXCR4 and alternative coreceptors. Phenotypic validation, together with distinct V3 loop signatures, provides evidence of viral adaptation to divergent tissue environments and highlights limitations of genotypic tropism prediction alone. These findings advance the understanding of HIV-1C pathogenesis and have implications for evaluating coreceptor usage in the context of entry inhibitor-based interventions particularly in regions where HIV-1C is endemic and diagnostic resources are limited.