TY - JOUR

T1 - T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy

AU - Lustig, Gila

AU - Cele, Sandile

AU - Karim, Farina

AU - Derache, Anne

AU - Ngoepe, Abigail

AU - Khan, Khadija

AU - Gosnell, Bernadett I.

AU - Moosa, Mahomed Yunus S.

AU - Ntshuba, Ntombi

AU - Marais, Suzaan

AU - Jeena, Prakash M.

AU - Govender, Katya

AU - Adamson, John

AU - Kløverpris, Henrik

AU - Gupta, Ravindra K.

AU - Harrichandparsad, Rohen

AU - Patel, Vinod B.

AU - Sigal, Alex

N1 - Publisher Copyright: © 2021 Lustig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1371/journal.ppat.1009871

DO - 10.1371/journal.ppat.1009871

M3 - Journal article

C2 - 34555123

AN - SCOPUS:85116020670

VL - 17

JO - P L o S Pathogens

JF - P L o S Pathogens

SN - 1553-7366

IS - 9

M1 - e1009871

ER -