HIV-1 detection in the olfactory mucosa of HIV-1 infected participants

OBJECTIVE: Human Immunodeficiency virus (HIV) infection chronically affects the central nervous system (CNS). Olfactory mucosa (OM) is a unique site in the respiratory tract that is directly connected to the CNS, thus we wanted to evaluate OM as a surrogate of CNS sampling. DESIGN: We conducted a preliminary study examining HIV populations and susceptible cells in the OM. METHODS: OM was sampled by minimally invasive brushing. CSF analyses were performed as per routine clinical procedures. OMP, CD4, CD8 and TAT expressions were assessed by immunohistochemistry. Plasma, CSF and OM HIV-RNA were quantified using the CAP/CTM assay, while HIV proviral DNA was evaluated on PBMC and OM. HIV-1 env deep sequencing was performed for phylogenetic analysis. RESULTS: 88.2% of ART naive participants (15/17) and 21.4% of ART treated participants (6/28) had detectable HIV-RNA in samples from their OM; CSF escape was more common in patients with OM escape (50% vs. 7.9%, p\u200a=\u200a0.010). OM samples contained few cells positive for CD4, CD8 or HIV-DNA and no HIV TAT-positive cells, indicating that this approach efficiently samples virions in the OM, but not HIV-infected cells. Yet, using a deep sequencing approach to phylogenetically compare partial HIV env genes in five untreated participants, we identified distinct viral lineages in the OM. CONCLUSIONS: The results of this study suggest that nasal brushing is a safe and useful technique for sampling the olfactory mucosa. HIV RNA was detected in most na\uefve and in some treated patients warranting larger longitudinal studies