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. 

The post Persistent HIV in Cerebrospinal Fluid Associated with Cognitive Impairment appeared first on MyMedicPlus.

Investigators from the AIDS Clinical Trials Group (ACTG), the world’s largest and longest-established HIV research network, today announced that the Journal of Clinical Investigationpublished new findings from the ACTG HIV Reservoirs Cohort Study (A5321). The study found that HIV DNA remained in the cerebrospinal fluid of half of participants with well-managed HIV (virologic suppression in the plasma), confirming that the central nervous system (CNS) is a major reservoir for latent HIV. Individuals who harbored HIV DNA in the cerebrospinal fluid were more likely than other study participants to experience cognitive deficits on neurocognitive testing.

“The persistence of HIV in sanctuary sites in the human body, even in the presence of long-term therapy, is a challenge to HIV remission and cure that the ACTG is actively working to address,” said ACTG Chair Judith Currier, M.D., MSc, University of California Los Angeles. “Because neurocognitive function can be compromised even in individuals whose HIV is well treated, it is very important that we understand HIV persistence in the CNS so that we can develop strategies to treat it. This study provides preliminary insights into these challenges.”

This substudy in the ACTG HIV Reservoirs Cohort Study (A5321) was led by Serena Spudich, M.D., Yale University, the late Kevin Robertson, Ph.D., University of North Carolina at Chapel Hill, and John Mellors, M.D., University of Pittsburgh. The study included 69 participants with well-treated HIV who had their cerebrospinal fluid and blood collected and underwent neurocognitive assessments, which included tests of memory, learning, motor function, and more. Participants were mostly male (97 percent) and had been on HIV treatment for a median of almost nine years, with a good response to medications (HIV viral loads in the plasma were all <100 copies/mL and median CD4 counts were in the normal range). Using highly sensitive methods to detect HIV, researchers found that almost half of these participants harbored viral DNA in cells found in the cerebrospinal fluid. Of those, 30 percent met the criteria for cognitive impairment.

While the study established an association between HIV DNA in cerebrospinal fluid with poorer performance on cognitive tests, researchers stressed that it did not establish a causal relationship, noting that there could be several explanations for the findings. Further studies will help determine strategies to reverse this persistence and improve neurological functioning in individuals with long-standing HIV.

The post Persistent HIV DNA in spinal fluid may be associated with cognitive challenges appeared first on MyMedicPlus.