HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low viral load in cART naïve HIV-infected adult Zimbabweans

  • Kudakwashe Mhandire University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
  • Mqondisi Tshabalala University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
  • Lynn Sodai Zijenah University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
  • Tommy Mlambo University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
  • Doreen Zvipo Mhandire University of Cape Town, Cape Town, South Africa
  • Cuthbert Musarurwa University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
  • Kerina Duri University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
  • Hilda Tendisa Matarira University of Zimbabwe College of Health Sciences, Harare, Zimbabwe
  • Collet Dandara University of Cape Town, Cape Town, South Africa
  • Sarah L Rowland-Jones University of Oxford, Oxford, United Kingdom
  • Babill Stray-Pedersen University Hospital, Oslo, Norway
Keywords: HLA, KIR, natural killer cells, HIV, viral load, Zimbabweans

Abstract

Introduction: 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.

Methodology: 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.

Results: 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.

Conclusion: 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.

Author Biographies

Kudakwashe Mhandire, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe

Department of Chemical Pathology

Mqondisi Tshabalala, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe

Department of Immunology

Lynn Sodai Zijenah, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe

Department of Immunology

Tommy Mlambo, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe

Department of Immunology

Doreen Zvipo Mhandire, University of Cape Town, Cape Town, South Africa

Division of Human Genetics, Department of Clinical Laboratory Sciences

Cuthbert Musarurwa, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe

Department of Chemical Pathology

Kerina Duri, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe

Department of Immunology

Hilda Tendisa Matarira, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe

Department of Chemical Pathology

Collet Dandara, University of Cape Town, Cape Town, South Africa

Division of Human Genetics, Department of Clinical Laboratory Sciences

Sarah L Rowland-Jones, University of Oxford, Oxford, United Kingdom

Nuffield Department of Medicine

Babill Stray-Pedersen, University Hospital, Oslo, Norway

Institute of Clinical Medicine, University of Oslo and Womens’ Clinic, Rikshospitalet

Published
2018-12-31
How to Cite
1.
Mhandire K, Tshabalala M, Zijenah L, Mlambo T, Mhandire D, Musarurwa C, Duri K, Matarira H, Dandara C, Rowland-Jones S, Stray-Pedersen B (2018) HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low viral load in cART naïve HIV-infected adult Zimbabweans. J Infect Dev Ctries 12:1105-1111. doi: https://doi.org/10.3855/jidc.10848
Section
Original Articles