Genetic influence of CCR5, CCR2, and SDF1 variants on human immunodeficiency virus 1 (HIV-1)-related disease progression and neurological impairment, in children with symptomatic HIV-1 infection

The role that host genetics plays in the modification of the rate of human immunodeficiency virus 1 ( HIV-1) - related disease progression was evaluated in a seroprevalent cohort of 1049 children with symptomatic HIV- 1 infection who participated in 2 clinical trials in the United States. Variants including CCR2- V64I, CCR5-wt/ Delta32, CCR5- 59029- G/ A, CCR5- 59353- T/ C, CCR5- 59356- C/ T, and SDF1- 3'- G/ A were identified by polymerase chain- reaction genotyping. Children with the CCR5- wt/Delta32 genotype experienced significantly delayed disease progression, including less neurocognitive impairment. In the CCR5- wt/ wt group, the most rapid disease progression was in those with the CCR5- 59029- A/ A genotype, which was present in 23% of the children. Although the SDF1- 3'- A/ A variant was associated with more- rapid disease progression, it occurred in < 2% of the children studied. Modest or little impact was associated with the CCR5- 59353, CCR5- 59356, or CCR2 genotypes. Thus, in children with the CCR5- wt/ wt genotype, variants at CCR5- 59029 have the broadest impact on disease progression. These data suggest that, in children, host genetics plays an important role in HIV- 1 related disease progression and neurological impairment.