Despite Long-Term ART Treatment, HIV Remains in Cerebrospinal Fluid, Associated With Neurocognitive Problems

After nearly a decade of adhering to treatment, cells harboring HIV could still be found in the cerebrospinal fluid of half of the participants.

New study findings are warning that despite years of antiretroviral therapy (ART) treatment, HIV persists in spinal fluid and is linked to cognition problems. The study of nearly 70 people living with HIV found that after nearly a decade of adhering to treatment, cells harboring HIV could still be found in the cerebrospinal fluid (CSF) of half of the participants.

The findings could offer important answers to a largely unanswered question of why some people with well-controlled infection still experience issues with memory, concentration, and the ability to complete complex tasks.

“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,” wrote the authors.

Among the 48% of participants with cell-associated HIV DNA in their CSF, 30% met criteria for cognitive impairment, compared with 11% of participants who did not have cells with HIV in their CSF.

The researchers did note that it’s not clear whether the presence of cell-associated HIV DNA is responsible for cognitive impairment, adding that there could be several explanations for these findings. For example, it’s possible that the amount of original infection in the nervous system was higher among participants with cells harboring HIV in the CSF or that the development of cognitive problems began early in HIV infection before initiation of ART.

“I don’t know of a single infectious disease that is easier to treat when it’s in the brain than when it’s elsewhere in the body, “ John Mellors, MD, professor and chief of the University of Pittsburgh School of Medicine’s Division of Infectious Diseases, and senior author of the study, said in a statement. “It is difficult to target infections that lurk in the brain and HIV is probably not an exception to the rule. We have our work cut out for us in the quest for an HIV cure, but knowing is half the battle, so I’m cautiously optimistic.”

The 69 participants enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study underwent concurrent lumbar puncture, phlebotomy, and neurocognitive assessment. They had all been receiving treatment for an average of 9 years. Following assessment of CSF, the researchers identified cell-free HIV RNA in 4% and cell-associated HIV DNA in 9%. These low rates suggest low levels of HIV transcription within cells and infrequent release into the extracellular space while on ART.


Spudich S, Robertson K, Bosch R, et al. Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance [published online July 15, 2019]. J Clin Invest. doi: 10.1172/JCI127413.

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