TRIM5α 136Q, CCR5 Promoter 59029G And CCR264I Alleles Impact The Progression Of HIV In Children And Adolescents.

Abstract

BackgroundChildren show various degrees of vulnerability regarding HIV infection and disease progression. This disparity presents challenges for the follow-up of infected children. Here we investigated reasons behind this variability focusing on some host-related HIV genes.MethodsWe screened 570 Cameroonian children and adolescents, aged 1 to 19 years old. Among them, 137 were followed over 4 years, from 2010 to 2015. Upon signing a proxy consent, children and adolescents were classified according to their age, CD4 count, viral load and clinical symptoms as long-term non-progressors (LTNP), slow progressors (SP) and rapid progressors (RP). Their blood was collected every 6 months and used for biological and host genetic polymorphism analyses. Five genes were genotyped: Trim5α (R136Q), CCR5 promoter 59029G, CCR2-64I, SDF 3ʹA and CCR5-Δ32. Exposed non-infected (HEU) and unexposed HIV negative children (HNEU) were recruited as control groups.ResultsAmong the 5 genes studied, the protective allele of Trim5α (R136Q) was present in all LTNP and in 72.34% and 2.56% of SP and RP, respectively (p<0.0001). The CCR5 promoter 59029G/G was also more present in LTNP and SP than in RP (p=0.02; p=0.04). The protective CCR2-64I homozygous genotype was almost absent in all groups, only the heterozygous genotype was present with a significant difference between RP vs SP (p=0.0001), and SP vs LTNP (p=0.0002). The CCR2-∆32 was completely absent either as homozygous or heterozygous genotype. It was a monomorphic allele. SDF 3ʹA was almost present as homozygous wild-type genotype in our study population and was associated neither to disease acquisition nor to disease progression.ConclusionAmong the 5 genes described in the study, Trim 5α (R136Q), CCR5 promoter 59029G and CCR2V64I alleles were associated to the progression of HIV infection in children and adolescents.