Five of seven previous genome-wide association studies (GWAS) of HIV acquisition incorporated measurements of HIV exposure (mother-to-child transmission,[6] serodiscordant heterosextual couples,[7] clinic-based recruitment for sexually transmitted infections (STIs),[8] recruitment of HIV- sex workers,[9] and hemophiliacs with probable exposure[10]), however the studies’ sample sizes were small (n = 226–1,379).[6–10] The two other GWAS of HIV acquisition achieved the largest samples sizes (n = 1,837 and13,851) but used population-based controls who were unlikely to have been exposed to HIV-1.[11,12] None of these prior GWAS identified replicable genes contributing to HIV susceptibility. [1,2,12] Thus, since its discovery in 1996, a 32-base pair deletion in the CCR5 gene remains the only genetic variant conclusively associated with HIV acquisition.[12–14] Identifying additional genetic associations with HIV acquisition is important to understanding the pathogenesis of HIV-1 and providing targets for medication and vaccine development[1,15] as illustrated by CCR5Δ32 giving rise to an antiretroviral drug inhibiting viral entry (maraviroc).[13,14]
