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AIDS. 2019 Mar 15;33(4):665-674. doi: 10.1097/QAD.0000000000002102.

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

Author information

1
Unit of Pathology, Department of Medical Sciences, University of Torino, Torino, Italy.
2
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
3
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino.
4
Laboratory of Microbiology and Molecular Biology, Ospedale Amedeo di Savoia.
5
Unit of Otorhinolaryngology, Ospedale Maria Vittoria.
6
Unit of Neurology, Ospedale Maria Vittoria, ASL 'Città di Torino', Torino.
7
Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.

Abstract

OBJECTIVE:

HIV infection chronically affects the central nervous system (CNS). Olfactory mucosa is a unique site in the respiratory tract that is directly connected to the CNS; thus we wanted to evaluate olfactory mucosa as a surrogate of CNS sampling.

DESIGN:

We conducted a preliminary study examining HIV populations and susceptible cells in the olfactory mucosa.

METHODS:

Olfactory mucosa was sampled by minimally invasive brushing. Cerebrospinal fluid (CSF) analyses were performed as per routine clinical procedures. Olfactory marker protein, CD4, CD8, and trans-activator of transcription (TAT) expressions were assessed by immunohistochemistry. Plasma, CSF, and olfactory mucosa HIV-RNA were quantified using the Cobas AmpliPrep/Cobas TaqMan assay, whereas HIV proviral DNA was evaluated on peripheral blood mononuclear cell and olfactory mucosa. HIV-1 env deep sequencing was performed for phylogenetic analysis.

RESULTS:

Among ART-naive participants, 88.2% (15/17), and among ART-treated participants, 21.4% (6/28) had detectable HIV-RNA in samples from their olfactory mucosa; CSF escape was more common in patients with olfactory mucosa escape (50 vs. 7.9%; P = 0.010). Olfactory mucosa 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 olfactory mucosa, 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 well tolerated and useful technique for sampling the olfactory mucosa. HIV-RNA was detected in most naïve and in some treated patients, warranting larger longitudinal studies.

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