15th Annual Conference of the British HIV Association 1-3 April 2009, Liverpool, UK

THE ROLE OF THE GUT MUCOSA IN PROTECTION FROM HIV-1 IN HIGHLY EXPOSED PERSISTENTLY SERONEGATIVE INDIVIDUALS (HEPS)

HIV Med 2009 Apr 1-3 (Suppl 1);15:9 (abstract no. O16)

J Fox¹, C Willberg², P Ziprin³, R Goldin³, J Weber³, M McClure³, P Klenerman² and S Fidler^3
1Guys and St Thomas’ NHS Trust, London, UK, ²University of Oxford, Oxford, UK, ³Imperial NHS Trust, London, UK

AIM: To determine whether individuals who are exposed to HIV but remain seronegative have HIV-1 specific immune responses or evidence of low level HIV-infection in the gut.

METHODS: Rectal tissue and Peripheral Blood Mononuclear Cell (PBMC) from 6 HEPS and their HIV-1 infected partners were compared to gut resection samples from 6 HIV-1 unexposed uninfected (UU) controls undergoing surgical procedures for clinical indications. Cytokine production by extracted lymphocytes from blood and rectal tissue following in vitro stimulation with HIV-1 gag was assessed using Luminex and HIV detected by ultrasensitive HIV DNA PCR on CD4 selected cells. Tissue architecture and cell populations were evaluated using immunohistochemisrty. All laboratory investigations were performed blinded to HIV status. Detailed sexual behaviour was collected from all couples.

RESULTS: Compared to control rectal tissue, HEPS had significantly less CD8 staining and a trend towards increased CD16 staining, particularly in those reporting most risk behaviour. HIV was not detected in the rectal mucosa or PBMCs of HEPS or UU either by PCR or p24 staining. HIV specific immune responses were not identified in either the blood or rectal tissue of HEPS but were present in their HIV-infected partners.

CONCLUSIONS: This is the first study of the rectal tissue of HEPS and although limited by sample size, provides insight into gut HIV pathogenesis. The rectum does not represent a sanctuary site for viral control or harbour HIV-specific immune responses in HEPS. Flow cytometry is required to investigate CD8 and CD16 cell populations further. The trend towards increased CD16 in HEPS with increasing sexual exposure to HIV is intriguing as CD16 is found on the surface of NK cells, monocytes and macrophages which play a vital role in the first line of defence against HIV infection.

(BHIVA Research Award Winner 2006: The role of gut mucosa in protection from HIV. Julie Fox)

2009-04-01
O16

Copyright © 2009 - British HIV Association (BHIVA) Reproduction of this abstract (other than one copy for personal reference) must be cleared through the BHIVA Organising Secretariat 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD