Abstract
The central nervous system HIV reservoir is incompletely understood and is a major barrier to HIV cure. We profiled people with HIV (PWH) and uninfected controls through single-cell transcriptomic and T cell receptor (TCR) sequencing to understand the dynamics of HIV persistence in the CNS. In PWH on ART, we found that most participants had single cells containing HIV-1 RNA, which was found predominantly in CD4 central memory T cells, in both cerebrospinal fluid (CSF) and blood. HIV-1 RNA–containing cells were found more frequently in CSF than blood, indicating a higher burden of reservoir cells in the CNS than blood for some PWH. Most CD4 T cell clones containing infected cells were compartment specific, while some (22%) — including rare clones with members of the clone containing detectable HIV RNA in both blood and CSF — were found in both CSF and blood. These results suggest that infected T cells trafficked between tissue compartments and that maintenance and expansion of infected T cell clones contributed to the CNS reservoir in PWH on ART.
Authors
Meng Wang, Jennifer Yoon, Hailey Reisert, Bibhuprasad Das, Benjamin Orlinick, Jennifer Chiarella, Elias K. Halvas, John Mellors, Alina P.S. Pang, Lydia Aoun Barakat, Margaret Fikrig, Joshua Cyktor, Yuval Kluger, Serena Spudich, Michael J. Corley, Shelli F. Farhadian
