Abstract
Polymorphisms in killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) gene families are implicated in differential outcomes of HIV infection. However, research findings on the influence of KIR and HLA-C polymorphism on HIV disease progression remain inconclusive. We thus investigated the association of KIR and HLA-C gene polymorphisms with plasma HIV load (VL) and CD4+ T lymphocyte (CD4) count in 183 chronically HIV-infected, combination antiretroviral therapy (cART) naïve Zimbabweans of Bantu origin. The presence or absence of 15 KIR genes were determined using sequence specific primer polymerase chain reaction while HLA-C typing was performed using chain termination DNA sequencing. Plasma VL was determined using the Cavidi Exavir viral load version 3 assay while CD4+ T lymphocytes were enumerated using flow cytometry. VLs and CD4 counts were compared between gene/genotype carriers and non-carriers using Mann-Whitney ranksum test. HLA-C*18:01 allele carriers had a significantly lower median log10 VL (2.87copies/mL [IQR;2.3-3.2]) than the non-C*18:01 carriers (3.33copies/mL [IQR; 2.74-3.9]), p = 0.018. Further, median log10 VL was significantly lower in KIR2DL2+C1 carriers (2.745 [IQR; 2.590-2.745]) than non-KIR2DL2+C1 carriers (3.4 [IQR; 2.746-3.412]), p = 0.041. Comparison of CD4 + T lymphocyte counts between C*08:02 allele carriers and non-C*08:02 carriers showed a significantly higher median CD4 count in C*08:02 carriers (548cells/µL [IQR;410-684]) than in non-carriers (428cells/µL [IQR;388-537]), p = 0.034. We conclude that the HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low VL while the C*08:02 is associated with high CD4+ T lymphocyte count among cART naïve Zimbabwean adults with chronic HIV infection.
Highlights
Polymorphisms in killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) gene families are implicated in differential outcomes of HIV infection
HLA act as ligands for killer cell immunoglobulin-like receptors (KIR) that are expressed on natural killer (NK) cells [7]
Of the 18 HLA-C alleles detected in >1% of the study population, carriage of the C*18:01, an allele that is restricted to Africans, was associated with low VL compared to nonC*18:01 carriage (Supplementary Table 1)
Summary
Polymorphisms in killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) gene families are implicated in differential outcomes of HIV infection. We investigated the association of KIR and HLA-C gene polymorphisms with plasma HIV load (VL) and CD4+ T lymphocyte (CD4) count in 183 chronically HIV-infected, combination antiretroviral therapy (cART) naïve Zimbabweans of Bantu origin. Gene association studies of markers of HIV disease progression (viral load [VL] and CD4+ T lymphocyte count [CD4 count]) show that polymorphisms in the human leukocyte antigen (HLA) gene family are among the most potent determinants of HIV disease progression [3]. HLA class I molecules, expressed on nucleated cells are involved in the presentation of HLA bound HIV derived peptides to cytotoxic T-lymphocytes (CTLs) [6] This antigen presentation stimulates cytotoxic activity of the CD8+ T lymphocytes which destroys the HIV infected cells. HLA act as ligands for killer cell immunoglobulin-like receptors (KIR) that are expressed on natural killer (NK) cells [7]
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