HIV may persist in the central nervous system (CNS) despite treatment with antiretroviral therapy (ART), which could lead to cognitive impairment, according to a new study published in the Journal of Clinical Investigation. 

Most HIV research has focused on blood CD4+ memory T cells as the major viral reservoir; however, HIV persists in other sites, such as mucosal lymphoid tissue, bone marrow, and the brain, where infection can lead to CNS manifestations. 

According to the study authors, large studies of cerebrospinal fluid (CSF) cells in participants on ART who have suppressed plasma HIV RNA levels have not been previously performed. 

For the study, the researchers assessed HIV persistence in CSF and the associations with inflammation and cognitive performance during long-term ART. The study included mostly men aged 45 to 66 years who have had their infections controlled with ART for an average of 9 years. To assess HIV persistence, the researchers analyzed each individual’s CSF for HIV DNA and then compared the data to each of their results from standard neurocognitive evaluations. 

Overall, approximately half of the study participants had viral DNA in cells in the CSF, suggesting the presence of latent virus. However, only 4% of participants had detectable HIV RNA in cell-free CSF fluid, according to the findings. Additionally, 30% of those with persistent HIV DNA in the CSF experienced clinical neurocognitive impairment compared with 11% of individuals whose CSF did not contain viral DNA. The researchers did not correlate CSF inflammatory biomarkers with HIV persistence. 

“The striking observation that almost half of participants harbored HIV-infected cells in the CSF demonstrates that the CNS compartment is a site of viral persistence despite many years of viremia suppression on ART,” the authors wrote in the study. 

Although the findings indicate that persistent HIV-infected cells in the CNS may contribute to neurocognitive impairment, the authors noted that the overall frequency of cognitive impairment in this group was relatively low. Still, the study demonstrated a higher-than-expected prevalence of persistent HIV in the CNS, pointing to continued obstacles in the complete eradication of HIV from the body. 

“Our study indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART,” the researchers wrote. 

Furthermore, sensitive methods of HIV detection combined with more research of CSF cells can help provide more insight into the CNS reservoir of HIV, the authors concluded. 

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