Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus

• DOI: 10.1038/s41564-022-01306-6
• Publication Date: 2023-01-31T12:26:28Z
• Authors: Laura P. Kincer; Sarah Beth Joseph; Maria M. Gilleece; Blake M. Hauser; Sabrina Sizemore; Shuntai Zhou; Clara Di Germanio; Henrik Zetterberg; Dietmar Fuchs; Steven G. Deeks; Serena Spudich; Magnus Gisslen; Richard W. Price; Ronald Swanstrom
• Keywords: Pediatric; Central Nervous System; Pediatric AIDS; 0303 health sciences; T-Lymphocytes; Neurosciences; HIV Infections; Biological Sciences; Microbiology; Antiviral Agents; 3. Good health; 03 medical and health sciences; Infectious Diseases; Good Health and Well Being; Medical Microbiology; HIV-1; HIV/AIDS; 2.2 Factors relating to the physical environment; Humans; Aetiology; Infection

HIV-1 persists as a latent reservoir in people receiving suppressive antiretroviral therapy (ART). When ART is interrupted (treatment interruption/TI), rebound virus re-initiates systemic infection in the lymphoid system. During TI, HIV-1 is also detected in cerebrospinal fluid (CSF), although the source of this rebound virus is unknown. To investigate whether there is a distinct HIV-1 reservoir in the central nervous system (CNS), we compared rebound virus after TI in the blood and CSF of 11 participants. Peak rebound CSF viral loads vary and we show that high viral loads and the appearance of clonally amplified viral lineages in the CSF are correlated with the transient influx of white blood cells. We found no evidence of rebound macrophage-tropic virus in the CSF, even in one individual who had macrophage-tropic HIV-1 in the CSF pre-therapy. We propose a model in which R5 T cell-tropic virus is released from infected T cells that enter the CNS from the blood (or are resident in the CNS during therapy), with clonal amplification of infected T cells and virus replication occurring in the CNS during TI.