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Background  HLA class I molecules are ligands for killer cell immunoglobin like receptors (KIR) that control the antiviral response of natural killer (NK) cells. However, the effects of  KIR  and  HLA  ( KIR/HLA ) alleles on HIV disease of children have not been studied.    Methods  993 antiretroviral naïve children with symptomatic HIV infection from PACTG protocols P152 and P300 were genotyped for  KIR  and  HLA  alleles using the Luminex platform. Linear regression was used to test the association between genotypes and baseline pre-ART HIV RNA, CD4 +  lymphocyte count, and cognitive score, adjusting for age, race/ethnicity and study. The interaction between genetic markers and age was investigated. To account for multiple testing the false discovery rate (FDR) was controlled at 0.05.    Results  Children with the  KIR2DS4*ALL FULL LENGTH  ( KIR2DS4*AFL ) allele had higher CD4 +  lymphocyte counts. Among children ≤2 years of age, the  KIR2DS4*AFL  was associated with lower plasma HIV RNA and higher cognitive index scores.  KIR Cent2DS3/5_1  had lower CD4 +  lymphocyte counts in children ≤2 years of age, while the presence of  Tel1 ,  Tel2DS4_2 ,  Tel2DS4_4 ,  Tel8 ,  Tel2DS4_6  had higher CD4 +  lymphocyte counts in all children. Presence of  Cent2 ,  Cent4 and Cent8  was associated with increased HIV RNA load in children ≤2 years. Presence of  KIR3DL1+Bw4  was associated with higher CD4 +  lymphocyte counts in all children. Among children >2 years old,  KIR3DS1+Bw4-80I  was associated with higher plasma HIV RNA, and  Bw6/Bw6  was associated with lower plasma HIV RNA compared to children with  KIR3DS1+Bw4-80I .    Conclusions  Presented data show for the first time that specific  KIR  alleles independently or combined with HLA ligands are associated with HIV RNA and CD4 +  lymphocyte counts in infected, antiretroviral naive children; and many of these effect estimates appear to be age dependent. These data support a role for specific  KIR  alleles in HIV pathogenesis in children.

Killer Cell Immunoglobulin-Like Receptor Alleles Alter HIV Disease in Children