Clinical parameters, selected HLA and chemokine gene variants associated with late presentation into care of people living with HIV/AIDS.

Abstract

Late presentation into care remains a significant problem in the diagnosis of HIV infection, and may negatively impact the Joint United Nations Program HIV/AIDS elimination targets. Host genetics affects the tempo of HIV disease progression and therefore may influence clinical status at care entry. Longitudinal data were collected for 863 Caucasian patients followed up at Pomeranian Medical University, Szczecin, Poland. Single nucleotide polymorphisms in CCR2 (rs1799864), CX3CR1 (rs3732378), HLAC-35 (rs9264942), CCR5 promoter (rs1799988) as well as 32 base pair CCR5 mutation and HLA-B*5701 genotypes were correlated with the clinical and immunologic patient status at care entry. Late presentation was defined as baseline CD4 lymphocyte count <350 cells/μL or history of AIDS-defining illness, while advanced HIV disease as baseline CD4 lymphocyte count <200 cells/μL or AIDS. Of the analyzed gene variants, the CCR2 (rs1799864) GG genotype was more frequent among patients presenting for care with a CD4 lymphocyte count <200/μL (82.6% for GG homozygotes vs. 74.5% for allele A carriers, p=0.01). The presence of the heterozygous wt/Δ32 genotype at the CCR5 gene was associated with a higher frequency of asymptomatic infection (18.9% for wt/Δ32 heterozygotes vs. 12% for wt/wt homozygotes, p=0.03). As expected, this association was also observed among late presenters compared to patients presenting for care earlier (13.7% vs. 19,7%, respectively, p=0.04). Finally, HLA-B*5701 was less common among late presenters (5%) compared to patients who entered care early (9.6%, p=0.01) or patients with advanced HIV disease (8.9% vs. 5.2%, p=0.02). Late presentation was associated with the GG homozygous genotype at the CCR2 rs1799864 SNP, while both the HLA-B*5701 variant and the CCR5 wt/Δ32 were associated with more favorable clinical profile at care entry.