Full reservoirs and poor adherence: two cases of symptomatic HIV cerebrospinal fluid escape with tenofovir alafenamide/emtricitabine/bictegravir

Background: – Symptomatic cerebrospinal fluid (CSF) escape is an uncommon presentation in people with HIV with undetectable or low-level HIV RNA while on combination antiretroviral treatment (cART). Only one case has been reported in a patient receiving bictegravir-based therapy so far.Methods: – We looked for patients presenting with neurological symptoms while on Tenofovir Alafenamide/Emtricitabine/Bictegravir and who were confirmed to have a CSF HIV RNA above plasma HIV RNA. Results: – One patient presented with confusion and cognitive changes; her plasma and CSF HIV RNA were 486 and 1400 copies/ml. In CSF but not plasma, next-generation sequencing identified resistance-associated mutations (RAMs) to nucleoside reverse transcriptase inhibitors (K70N at 22% and T215S at 92%) and nonnucleoside reverse transcriptase inhibitors (E138K at 18%). One patient presented with lower limb pain and weakness: his plasma and CSF HIV RNA were 7410 and 88 000 copies/ml. No RAMs were found but biomarkers suggested intrathecal immune activation and neuronal damage. Intensification with doravirine led to suppression of plasma viremia within 3 months. Conclusion: – This case series suggests that symptomatic CSF escape is possible even with modern cART and that lumbar punctures may be needed in the presence of unexplained neurological/neuropsychological symptoms.