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.
Highlights
HIV persistence in the face of antiretroviral therapy (ART) necessitates lifelong adherence to treatment
We sampled cerebrospinal fluid (CSF) and matched blood from participants living with HIV (n = 156) clinically indicated for lumbar puncture as part of their diagnostic workup in Durban, South Africa (Table 1)
We examined the cellular source of viremia in study participants with CSF escape in Durban, South Africa, and whether drug levels in the CSF are lower in individuals with CSF escape versus those suppressed both in the blood and CSF
Summary
HIV persistence in the face of ART necessitates lifelong adherence to treatment. The CNS may serve as one reservoir for HIV persistence [1]. Consistent with a role for the CNS as an HIV reservoir, a subset of individuals show CSF escape, where HIV is detectable in the CSF while being successfully suppressed below the level of detection in the blood [11,12,13,14,15,16]. Potential reasons for a CNS reservoir include reduced drug levels. Since the majority of individuals do not show detectable virus in the CSF, these lowered ART levels seem to be sufficient to suppress viremia. It is unclear if ART levels in the CSF are lower in individuals with neurosymptomatic CSF escape in South Africa, accounting for the lack of effective suppression in this compartment and possibly evolution of drug resistance mutations. Mutations could include the M184V or M184I resistance mutation to FTC, a drug which would provide selective pressure since it has good penetration to the CNS [14, 20,21,22,23,24]
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