-Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans.

HIV-associated sensory neuropathy (HIV-SN) is a disabling complication of HIV disease and antiretroviral therapies (ART). Since stavudine was removed from recommended treatment schedules, the prevalence of HIV-SN has declined and associated risk factors have changed. With stavudine, rs1799964*C (TNF-1031) associated with HIV-SN in Caucasians and Indonesians but not in South Africans. Here, we investigate associations between HIV-SN and rs1799964*C and 12 other polymorphisms spanning and seven neighboring genes (the -block) in Indonesians ( = 202; 34/168 cases) and South Africans ( = 75; 29/75 cases) treated without stavudine. Haplotypes were derived using fastPHASE and haplotype networks built with PopART. There were no associations with rs1799964*C in either population. However, rs9281523*C in intron 10 of (alternatively ) independently associated with HIV-SN in Indonesians after correcting for lower CD4 T-cell counts and >500 copies of HIV RNA/mL (model = 0.0011, Pseudo = 0.09). rs4947324*T (between and ) independently associated with reduced risk of HIV-SN and African haplotype 1 (containing no minor alleles) associated with increased risk of HIV-SN after correcting for greater body weight, a history of tuberculosis and nadir CD4 T-cell counts (model: = 0.0003, Pseudo = 0.23). These results confirm -block genotypes influence susceptibility of HIV-SN. However, critical genotypes differ between ethnicities and with stavudine use.