12th Annual Conference of the British HIV Association 29 March–1 April 2006, Brighton, UK

A POLYMORPHISM REDUCING RANTES EXPRESSION IS ASSOCIATED WITH PROTECTION FROM DEATH IN HIV-POSITIVE UGANDANS

HIV Med 2006; 7(Suppl. 1):6 (abstract no. O24)

Graham Cooke¹, Kerrie Tosh¹, Patricia Ramaley¹, Pontiano Kaleebu², Jessica Nakiyingi², Christine Watera², Charles Gilks³, Neil French⁴, James Whitworth¹ and Adrian Hill^1
1 Wellcome Trust Centre for Human Genetics, Oxford, UK, ² Medical Research Council Programme on AIDS, Uganda Virus Research Unit, Entebbe, Uganda, ³ Imperial College, London, UK, ⁴ Liverpool School of Tropical Medicine, Liverpool, UK

BACKGROUND: HIV-1 utilises two key co-receptors to gain entry to CD4 cells. One of these receptors, CCR5, is a target for a new class of antiviral drugs. A number of endogenous ligands for this receptor exist, including RANTES (CCL5). A single genetic variant (INT1.1C), apparently upregulating RANTES activity, has been associated with accelerated disease progression in American cohorts and, it has been suggested, accounts for 37% of disease progression in Africans. We investigated the role of this variant in a Ugandan cohort.

METHODS: Seven hundred and ninety-four HIV-positive individuals were recruited from a cohort in Uganda between 1995 and 1998. Data were available for follow-up until 2001. Polymorphisms within the RANTES gene were typed in these populations.

RESULTS: HIV-positive individuals homozygous for the INT1.1C polymorphism, previously associated with low RANTES expression, were less likely to die when compared to other genotypes (HR 0.53 = 95%, CI 0.33–0.83, P=0.007).

CONCLUSIONS: This first report of a non-HLA genetic association with HIV-1/AIDS disease progression in an African population reveals a genetic effect different to that reported for African–Americans. The variant previously associated with disease progression is here associated with disease protection. These findings may impact therapeutic strategies targeting the RANTES pathway in HIV infection.

2006-03-29
O24

Copyright © 2006 - 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