HIV in the CSF: Where Does It Come From?

An analysis of viral sequences suggests that HIV in the cerebrospinal fluid may be produced by a separate population of cells located in the central nervous system.

In some HIV-infected patients on antiretroviral therapy (ART), virus can be detected in cerebrospinal fluid (CSF). Whether such virus is produced within the central nervous system (CNS) or originates in the periphery and invades the CNS — and whether the virus in the CSF is replicating and evolving — is unknown. To address these questions, investigators studied viral sequences from CSF and plasma in a group of patients on ART.

Single-genome sequencing of HIV was attempted on CSF samples from 17 patients who had suppressed plasma viral loads; amplicons for sequencing were generated for 8 of the 17 patients. The CSF viral sequences were compared with sequences of HIV obtained from plasma samples from the same eight patients. In addition, virus from these patients was sequenced from CSF and plasma collected before ART initiation (presuppression samples).

In five of six patients from whom HIV sequences could be obtained from presuppression samples, there was evidence of genetic compartmentalization between CSF and plasma virus populations. In patients from whom CSF and plasma sequences could be obtained during suppressive ART, the sequences did not cluster together. (Some of the CSF viral sequences were replication-incompetent hypermutants.) For patients who had CSF sequences available at several time points during ART, there was no evidence of viral evolution.


This intensive study reveals that HIV sequences in the cerebrospinal fluid differ from those in the plasma at presuppression and on-therapy time points. This finding is consistent with the hypothesis that HIV in the CSF during suppressive antiretroviral therapy is being produced by cells located within the central nervous system or, perhaps, represents a subset of the virus in the periphery that is transported into the CSF. The absence of viral evolution in CSF suggests no or little ongoing HIV replication. Because of the small number of patients from whom virus sequences could be obtained, however, testing of more patients is needed to draw a definitive conclusion regarding the origin of HIV in CSF; such studies are currently under way.


  1. Dahl V et al. An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy. J Infect Dis 2014 Feb 11; [e-pub ahead of print]. (