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.
Singh
Kumud K
KK
Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, La Jolla, California 92093-0672, USA.
Barroga
Charlene F
CF
Hughes
Michael D
MD
Chen
Jie
J
Raskino
Claire
C
McKinney
Ross E
RE
Spector
Stephen A
SA
D015526:AIDS Dementia Complex / Q000235:genetics*; D018791:CD4 Lymphocyte Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D019562:Viral Load
C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine