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- Title
T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy.
- Authors
Lustig, Gila; Cele, Sandile; Karim, Farina; Derache, Anne; Ngoepe, Abigail; Khan, Khadija; Gosnell, Bernadett I.; Moosa, Mahomed-Yunus S.; Ntshuba, Ntombi; Marais, Suzaan; Jeena, Prakash M.; Govender, Katya; Adamson, John; Kløverpris, Henrik; Gupta, Ravindra K.; Harrichandparsad, Rohen; Patel, Vinod B.; Sigal, Alex
- Abstract
HIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are responsible for CSF escape, we collected blood and CSF from 156 neurosymptomatic participants from Durban, South Africa. We observed that 28% of participants with an undetectable HIV blood viral load showed CSF escape. We detected host cell surface markers on the HIV envelope to determine the cellular source of HIV in participants on the first line regimen of efavirenz, emtricitabine, and tenofovir. We confirmed CD26 as a marker which could differentiate between T cells and macrophages and microglia, and quantified CD26 levels on the virion surface, comparing the result to virus from in vitro infected T cells or macrophages. The measured CD26 level was consistent with the presence of T cell produced virus. We found no significant differences in ART concentrations between CSF escape and fully suppressed individuals in CSF or blood, and did not observe a clear association with drug resistance mutations in CSF virus which would allow HIV to replicate. Hence, CSF HIV in the face of ART may at least partly originate in CD4+ T cell populations. Author summary: The brain may be a site where HIV persists despite antiretroviral therapy (ART). Persistence can manifest as cerebrospinal fluid (CSF) escape, where HIV is detectable in the CSF but not the blood in some individuals. The reasons for CSF escape are incompletely understood. Evidence from individuals mostly on second line protease inhibitor-based ART indicates that detectable HIV in this compartment may have acquired drug resistance. In this work we investigated HIV in blood and CSF of 156 participants from Durban, South Africa. We observed a very high prevalence of CSF escape of 28%. We aimed to find the cell type responsible for producing HIV in CSF escape and whether replication occurred because of lower CSF drug levels or because the virus has developed resistance to therapy. We found that at least some of the CSF HIV was produced by T cells, and that drug resistance was not always present. This suggests that at least part of the CSF HIV reservoir may be generated by either an infection mode not requiring drug resistance for viral replication, or by latently infected CD4+ T cells trafficking to and releasing HIV in the CSF without extensive viral replication taking place.
- Subjects
DURBAN (South Africa); ANTIRETROVIRAL agents; HIV; T cells; VIRAL load; CEREBROSPINAL fluid; CELL populations; DRUG resistance
- Publication
PLoS Pathogens, 2021, Vol 17, Issue 9, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1009871