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 = 0.010). 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 naïve and in some treated patients warranting larger longitudinal studies.
HIV-1 detection in the olfactory mucosa of HIV-1 infected participants
Zanusso, Gianluigi;
2019-01-01
Abstract
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 = 0.010). 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 naïve and in some treated patients warranting larger longitudinal studies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.