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

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.

Reversal of CSF HIV-1 Escape during Treatment of HIV-Associated Cryptococcal Meningitis in Botswana

“…HIV viral escape in the CNS has been well documented in individuals with HIV-associated neurocognitive disorders (HAND); however, there are conflicting reports on whether this is also seen in individuals with HIV-associated opportunistic infections such as cryptococcal meningitis [ 7 , 32 , 33 , 34 ]. In this study that compared CSF HIV-1 VL versus plasma HIV-1 VL in individuals with HIV-associated cryptococcal meningitis, we observed a substantial proportion of individuals experiencing CSF viral escape (32.3% with day 1 samples, 25.0% with day 7 and 3.0% with day 14 samples).…”

Reversal of CSF HIV-1 Escape During Treatment of HIV-Associated Cryptococcal Meningitis in Botswana

“…HIV viral escape in the CNS has been well documented in individuals with HIVassociated neurocognitive disorders (HAND); however, there are conflicting reports on whether this is also seen in individuals with HIV-associated opportunistic infections such as cryptococcal meningitis [7,[32][33][34]. In this study that compared CSF HIV-1 VL versus plasma HIV-1 VL in individuals with HIV-associated cryptococcal meningitis, we observed a substantial proportion of individuals experiencing CSF viral escape (32.3% with day 1 samples, 25.0% with day 7 and 3.0% with day 14 samples).…”

Biotypes of HIV-associated neurocognitive disorders based on viral and immune pathogenesis

“…HIV establishes CNS infection early in disease [30] and has been documented primarily not only in microglia [31,32] but also in astrocytes [17]. Some emerging evidence suggests that virus detected in the CSF during viral escape contains CD26, a marker expressed on activated T cells, and therefore, may be from CD4+ T cells [33 ▪ ]. However, it is unknown if the T cells are trafficking in from the periphery or are brain-resident.…”