The Search for a Genetic Factor Associating with Immune Restoration Disease in HIV Patients Co-Infected withMycobacterium tuberculosis

Abstract

BACKGROUND: Up to 43% of HIV-infected patients co-infected withMycobacterium tuberculosisexperience exacerbations of tuberculosis (TB) after commencing antiretroviral therapy (ART). These are termed immune restoration disease (IRD). It is unclear why individual susceptibility varies.OBJECTIVE: We investigate if single nucleotide polymorphisms (SNP) in genes encoding cytokines, chemokines and their receptors associate with development of an IRD event in patients of two different ethnicities.METHODS: DNA samples were available from small well-characterised groups of HIV patients treated in Cambodia (TB-IRD,n= 17; HIV+TB+controls, n = 55) and India (TB-IRD,n= 19; HIV+TB+controls,n= 43). HIV patients with a TB diagnosis but no evidence of IRD were included to control for susceptibility to TB per se. Sixteen SNP implicated in inflammation or mycobacterial disease were genotyped.RESULTS: Susceptibility to TB-IRD associated with carriage of TNFA-1031*T (rs1799964;P=0.05) and SLC11A1 D543N*G (rs17235409;P=0.04) in Cambodian patients and carriage of IL18-607*G (rs1946518;P=0.02) and VDR FokI (F/f)*T (rs10735810;P=0.05) in Indian patients.CONCLUSIONS: Associations between polymorphisms in immune-related genes and TB-IRD were found, but none were common across two ethnicities.