Neurocognitive outcomes in indonesians living with HIV are influenced by polymorphisms in the gene encoding purinergic P2X receptor 7

Abstract

The advent of effective antiretroviral therapy (ART) has decreased the prevalence and severity of HIV-associated neurocognitive disorders (HAND), but milder forms of HAND remain despite optimal treatment. Neuronal injury and loss due to inflammation may mediate HAND. P2X7R encodes purinergic P2X receptor 7 which influences neuroinflammatory pathways and carries polymorphisms associated with sensory neuropathy in HIV patients. We assessed associations between P2X7R polymorphisms and neurocognitive outcomes in Indonesian patients (n ​= ​59) as they commenced ART and after 3, 6 and 12 months. Z-scores were calculated over 5 domains using local controls and evaluated as continuous variables. Optimal linear regression models identified polymorphisms influencing attention, memory, executive function, motor speed and total cognitive function at each time point. rs504677 was associated with lower executive and motor speed Z-scores at 0, 3, 6, and 12 months, and with memory at 0 and 12 months. Memory was positively influenced by carriage of the rs208296 minor allele at 0, 3 and 6 months and by carriage of the rs208307 minor allele at 0 and 12 months. Higher attention Z-scores associated with carriage of minor alleles of rs1653598 after 0 and 12 months. These also positively influenced executive function and motor speed after 0–6 months. This study identifies polymorphisms in P2X7R which influence domain-specific neurocognitive outcomes in HIV+ ​Indonesians prior to and shortly after commencing ART. This implicates purinergic P2X receptor 7 in the pathogenesis of HAND.