Summary: HIV can persist in the nervous system, even when the virus is suppressed. Even when the virus is suppressed, neurocognitive problems associated with the infection can persist.
Many people with HIV on antiretroviral therapy (ART) have viral genetic material in the cells of their cerebrospinal fluid (CSF), and these individuals are more likely to experience memory and concentration problems, according to new data published online today in the Journal of Clinical Investigation. A study of 69 individuals on long-term ART found that nearly half of the participants had persistent HIV in cells in their CSF, and 30% of this subset experienced neurocognitive difficulties. These findings suggest that HIV can persist in the nervous system even when the virus is suppressed in a patient’s blood with medication.
Investigators from the University of North Carolina, the University of Pittsburgh, and Yale University studied participants enrolled in the AIDS Clinical Trials Group (ACTG) HIV Reservoirs Cohort Study. This primarily male group–aged 45 to 56–of long-term HIV survivors had infections controlled with ART for on average nine years. Researchers analyzed each participant’s CSF for HIV DNA and then compared these data to each participants’ results from standard neurocognitive evaluations. About half of participants had viral DNA in cells in the CSF, indicating the presence of latent virus, even though standard HIV RNA ‘viral load’ tests of the cell-free CSF fluid were positive in only 4% of participants. Investigators also found that 30% of individuals with persistent HIV DNA in the CSF experienced clinical neurocognitive impairment compared with 11% of individuals whose CSF did not contain viral DNA.
Many researchers hypothesize that HIV-related inflammation causes HIV-associated neurocognitive disorder (HAND). The new findings suggest that the presence of persistent HIV-infected cells in the central nervous system (CNS), despite long-term ART, may play a role in neurocognitive impairment. The authors note that the overall frequency of neurocognitive impairment in this group was relatively low and that the association does not confirm that HIV DNA causes HAND. Overall, the current study found that examining CSF cells revealed a higher-than-expected prevalence of persistent HIV in the CNS, which may be a significant obstacle to efforts to eradicate HIV from the body.
Funding: The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH), both parts of the National Institutes of Health.
Judith Lavelle – NIH/NIAID
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Original Research: Open access
“Persistent HIV-infected Cells in Cerebrospinal Fluid are Associated with Poorer Neurocognitive Performance”. S Spudich et al.
Journal of Clinical Investigation. doi:10.1172/JCI127413
Persistent HIV-infected Cells in Cerebrospinal Fluid are Associated with Poorer Neurocognitive Performance
BACKGROUND. Persistence of HIV in sanctuary sites despite antiretroviral therapy (ART) presents a barrier to HIV remission and may affect neurocognitive function. We assessed HIV persistence in cerebrospinal fluid (CSF) and associations with inflammation and neurocognitive performance during long-term ART.
METHODS. Participants enrolled in the AIDS Clinical Trials Group (ACTG) HIV Reservoirs Cohort Study (A5321) underwent concurrent lumbar puncture, phlebotomy, and neurocognitive assessment. Cell-associated HIV DNA and HIV RNA (CA-DNA, CA-RNA) were measured by quantitative PCR (qPCR). in peripheral blood mononuclear cells (PBMCs) and in cell pellets from CSF. In CSF supernatant and blood plasma, cell-free HIV RNA was quantified by qPCR with single-copy sensitivity, and inflammatory biomarkers were measured by enzyme immunoassay.
RESULTS. Sixty-nine participants (97% male, median age 50 years, CD4 696 cells/mm3, plasma HIV RNA <100 copies/mL) were assessed after a median 8.6 years of ART. In CSF, cell-free RNA was detected in 4%, CA-RNA in 9%, and CA-DNA in 48% of participants (median level 2.1 copies/103 cells). Detection of cell-free CSF HIV RNA was associated with higher plasma HIV RNA (P = 0.007). CSF inflammatory biomarkers did not correlate with HIV persistence measures. Detection of CSF CA-DNA HIV was associated with worse neurocognitive outcomes including global deficit score (P = 0.005), even after adjusting for age and nadir CD4 count.
CONCLUSION. HIV-infected cells persist in CSF in almost half of individuals on long-term ART, and their detection is associated with poorer neurocognitive performance.
FUNDING. This observational study, AIDS Clinical Trials Group (ACTG) HIV Reservoirs Cohort Study (A5321), was supported by the National Institutes of Health (NIAID and NIMH).