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

2018 ◽  
Vol 12 (12) ◽  
pp. 1105-1111
Author(s):  
Kudakwashe Mhandire ◽  
Mqondisi Tshabalala ◽  
Lynn Sodai Zijenah ◽  
Tommy Mlambo ◽  
Doreen Zvipo Mhandire ◽  
...  
Keyword(s):  
Viral Load ◽  
Hiv Infection ◽  
T Lymphocyte ◽  
Genetic Variants ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Gene Families ◽  
Cd4 Count ◽  
Kir Genes ◽  
Differential Outcomes

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.

scholarly journals Variations in KIR Genes: A Study in HIV-1 Serodiscordant Couples

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Vijay R. Chavan ◽  
Deepali Chaudhari ◽  
Swati Ahir ◽  
Zakiya Ansari ◽  
Preeti Mehta ◽  
...  
Keyword(s):  
Viral Load ◽  
Hiv Infection ◽  
Indian Population ◽  
Killer Cell ◽  
High Viral Load ◽  
Kir Genes ◽  
Discordant Couples ◽  
Spss Software ◽  
First Time ◽  
Anti Hiv

Background. NK cells have anti-HIV activity mediated through killer cell immunoglobulin-like receptors (KIRs). The current prospective cohort study evaluated whether variation in KIR genes is associated with HIV infection in discordant couples (DCs), where one spouse remains seronegative (HSN) despite repeated exposure to the HIV.Methods. KIR was genotyped using PCR SSP. Viral load and CD4 counts were estimated using commercially available reagents. Data were analyzed using SPSS software.Results. Among the 47 DCs, HSN spouses had significantly (P=0.006) higher frequencies of KIR3DS1. Regression analysis revealed significant (P=0.009) association of KIR2DS1 with low viral load. KIR2DS4 variant was associated (P=0.032) with high viral load. Three pairs of KIR genes were in strong LD in HSNs and two pairs in HSPs. There were 60 KIR genotypes, and 16 are reported the first time in the Indian population. Exclusive genotypes were present either in HSPs (N=22, 11 unique genotypes) or in HSNs (n=27, 9 unique genotypes).Conclusions. This study highlights for the first time in the Indian population an association of KIR genes in HIV infection where presence of exclusive and unique genotypes indicates possible association with either HIV infection or with protection.

EFFECT OF IMMUNOMODULATORY HERBAL MEDICINAL PREPARATIONS ON CD4 + LYMPHOCYTE COUNT AND TOTAL VIRAL LOAD IN HIV-INFECTED INDIVIDUALS

INDIAN DRUGS ◽  
2012 ◽  
Vol 49 (07) ◽  
pp. 42-48
Author(s):  
S. T. Tharakan ◽  
◽  
G Kuttan ◽  
R. Kuttan ◽  
M. Kesavan ◽  
...  
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Viral Load ◽  
Hiv Infection ◽  
T Lymphocyte ◽  
Lymphocyte Count ◽  
Clinical Status ◽  
Hiv Patients ◽  
Herbal Formulation ◽  
Hematological Analysis

This study was carried out to determine the effect of herbal medication on the clinical status of HIV infected persons especially on their CD4+ T lymphocyte count and viral load. The toxicity of the medication was also studied. 25 HIV positive individuals were taken for the study. They were treated with a herbal formulation developed in our centre, for one year. Patients were evaluated for their clinical status every month and CD4+ T lymphocyte and viral load every six months. Other parameters assessed were body weight, hematological analysis and hepatic and renal function tests. Body weight was found to be increased in 20 patients out of 25 who have undergone treatment. CD4+T lymphocyte count was increased in 15 patients and viral load was decreased in 20 patients. In six patients viral load was undetectable range. Administration of these medications significantly reduced, elevated interferon-? and tumor necrosis factor in HIV patients. Medication did not produce any toxicity in HIV patients, as it did not show any significant change in hepatic function, renal function and haematology. Administration of herbal preparation was found to reduce clinical symptoms produced by HIV infection. This herbal formulation was found useful therapeutically for the management of HIV infection and did not produce any toxicity.

scholarly journals Immunologic and Virologic Outcomes of Obese and Nonobese Incarcerated Adults on Antiretroviral Therapy for HIV Infection

2018 ◽  
Vol 17 ◽  
pp. 232595741775226
Author(s):  
Kristen L. Bunnell ◽  
Arwa Aldossari ◽  
Connor Perkins ◽  
Christopher Schriever ◽  
Thomas D. Chiampas ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cohort Study ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Body Mass ◽  
Cd4 Count ◽  
Virologic Suppression ◽  
Matched Cohort ◽  
Nonobese Patients

Background: Obesity is common among patients with HIV. The objective of this study was to characterize response to antiretroviral therapy (ART) in a cohort of obese incarcerated adults compared to a nonobese cohort. Methods: A retrospective matched cohort study was conducted in an HIV telemedicine clinic. Patients with body mass index (BMI) >30 kg/m2 who received the same ART with >95% adherence for at least 6 months were matched to nonobese patients by age, gender, ART, CD4 count, and viral load at baseline. Results: Twenty pairs were included, with an average BMI of 24 kg/m2 in the nonobese cohort and 35 kg/m2 in the obese cohort. No difference was observed in the proportion of patients who achieved virologic suppression or the change in CD4 count from baseline to 6 to 12 months. Conclusion: This study revealed no differences in immunologic recovery or virologic suppression between obese and nonobese patients in an adult correctional population.

scholarly journals What Determines Do-Not-Resuscitate Status in Critically Ill HIV Patients?

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S435-S435
Author(s):  
Shannon L Turvey ◽  
Anne Gregory ◽  
Sean Bagshaw ◽  
Wendy I Sligl
Keyword(s):  
Viral Load ◽  
Hiv Infection ◽  
Critically Ill ◽  
Severity Of Illness ◽  
Cd4 Count ◽  
Apache Ii Score ◽  
Do Not Resuscitate ◽  
Hiv Patients ◽  
Icu Admission ◽  
First Time

Abstract Background Mortality and morbidity of people living with HIV have declined in the era of combination antiretroviral therapy (cART). However, Intensive Care Unit (ICU) admission rates remain high. In this study, we identified predictors of Do-Not-Resuscitate (DNR) status in critically ill HIV patients. Methods Retrospective cohort study of all first-time admissions of HIV-infected patients to five ICUs in Edmonton, Alberta from 2002 to 2014. Data collected included demographics, comorbidities, markers of HIV disease severity and control, admission diagnoses, severity of illness, organ failure, and DNR status. Multivariable logistic regression analysis was performed to identify factors associated with DNR status. Results During the study period, 282 patients were admitted to the ICU for the first time. Mean (SD) age was 44 (±10) years, 169 (60%) were male, 134 (48%) aboriginal, 153 (55%) co-infected with hepatitis C virus, and 184 (65%) had a history of polysubstance use. Median (IQR) CD4 count and viral load were 125 (30–300) cells/mm3and 28,000 (110–270,000) copies/mL, respectively. Only 98 (35%) patients were receiving cART at the time of admission while 45 (16%) were newly diagnosed in the ICU. Most common admission diagnosis was sepsis 189 (64%), 213 (76%) received mechanical ventilation, 133 (47%) vasopressor support and 35 (12%) renal replacement therapy. Sixty-seven (24%) patients were DNR and support was withdrawn in 42 (15%). In multivariable analysis, APACHE II score (adjusted odds ratio [aOR] 1.13; 95% CI, 1.08–1.19, P < 0.001), coronary artery disease (CAD) (aOR 5.7; 95% CI, 1.2–27.8, P = 0.03), prior opportunistic infection (OI) (aOR 2.6; 95% CI, 1.2–5.6, P = 0.015) and duration of HIV infection (aOR 1.07 per year; 95% CI, 1.01–1.14, P = 0.025) were independently associated with DNR status. Other factors such as ethnicity, HIV risk factor(s), CD4 count and viral load were not associated with DNR status. Conclusion In this relatively young cohort, one in four patients had DNR status during ICU admission. DNR designation was associated with severity of illness, along with CAD, prior OI, and duration of HIV infection. Future work should characterize the timing of patient DNR orders relative to ICU admission and describe patient and provider-specific factors that may influence decision-making towards DNR status. Disclosures All authors: No reported disclosures.

scholarly journals HLA Alleles and KIR Genes in Romanian Patients with Chronic Hepatitis C

2020 ◽  
Author(s):  
Larisa Ursu ◽  
Bogdan Calenic ◽  
Mircea Diculescu ◽  
Alina Dima ◽  
Ileana Constantinescu
Keyword(s):  
Hepatitis C ◽  
Nk Cells ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Hcv Infection ◽  
Hla Alleles ◽  
Kir Genes ◽  
Hla Ligands ◽  
Chronic Hcv

Background and Aims: The role of natural killer (NK) cells in the defense against hepatitis C virus (HCV) infection involve both innate and adaptive immunity. NK cells express a large panel of inhibitory and activating receptors who bind human leukocyte antigen (HLA) class I receptors. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic of these receptors being encoded by genes distributed differently in unrelated individuals. The aim of this study was to look at the immune response in chronic HCV patients by assessing NK-KIR genes and their corresponding HLA ligands. Methods: We genotyped 127 chronically HCV-infected patients and 130 non-infected healthy individuals for both KIR genes and their HLA ligands. The HLA-A, HLA-B, HLA-C genotypes were analyzed using polymerase chain reaction high-resolution typing. Results: KIR2DL3, KIR2DL5, KIR2DS4 norm, KIR3DL3, KIR2DP1, KIR3DP1 genes were significantly increased in the HCV group compared to healthy individual. Analysis of various HLA haplotypes revealed different HLA alleles associated with increased susceptibility to HCV infection. Thus, HLA A*23:01 was more frequent in the patients’ group than in the controls (p=0.030). At the same time HLA B*44:02 and C*04:02 were significantly elevated in HCV-positive patients (p=0.008 and respectively p= 0.007). Conclusions: These results suggest that the expression of KIR2DL3, KIR2DL5, KIR2DS4 norm, KIR3DL3 genes and the association with HLA alleles such as HLA A*23:01, B*44:02, C*04:02 may increase the patient susceptibility to chronic HCV infection.

scholarly journals Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

2019 ◽  
Vol 20 (3) ◽  
pp. 546 ◽  
Author(s):  
Dominika Deborska-Materkowska ◽  
Agnieszka Perkowska-Ptasinska ◽  
Anna Sadowska-Jakubowicz ◽  
Jolanta Gozdowska ◽  
Michał Ciszek ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Transplant ◽  
Viral Infections ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Infectious Complications ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection ◽  
Kir Genes

Infection with cytomegalovirus (CMV) remains a major problem in kidney transplant recipients, resulting in serious infectious complications and occasionally mortality. Accumulating evidence indicates that natural killer cell immunoglobulin-like receptors (KIRs) and their ligands affect the susceptibility to various diseases, including viral infections (e.g., CMV infection). We investigated whether KIR genes and their ligands affect the occurrence of CMV infection in a group of 138 kidney transplant recipients who were observed for 720 days posttransplantation. We typed the recipients for the presence of KIR genes (human leukocyte antigen C1 [HLA-C1], HLA-C2, HLA-A, HLA-B, and HLA-DR1) by polymerase chain reaction with sequence-specific primers. The multivariate analysis revealed that the lack of KIR2DS2 (p = 0.035), the presence of KIR2DL3 (p = 0.075), and the presence of KIR2DL2–HLA-C1 (p = 0.044) were risk factors for posttransplant CMV infection. We also found that a lower estimated glomerular filtration rate (p = 0.036), an earlier time of antiviral prophylaxis initiation (p = 0.025), lymphocytopenia (p = 0.012), and pretransplant serostatus (donor-positive/recipient-negative; p = 0.042) were independent risk factors for posttransplant CMV infection. In conclusion, our findings confirm that the KIR/HLA genotype plays a significant role in anti-CMV immunity and suggest the contribution of both environmental and genetic factors to the incidence of CMV infection after kidney transplantation.

Killer immunoglobulin-like receptor locus polymorphisms in multiple sclerosis

2011 ◽  
Vol 18 (7) ◽  
pp. 951-958 ◽  
Author(s):  
Ilijas Jelčić ◽  
Katharine C Hsu ◽  
Kristina Kakalacheva ◽  
Petra Breiden ◽  
Bo Dupont ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Risk ◽  
Age Of Onset ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Population Based ◽  
Class I ◽  
Kir Genes ◽  
Hla Class I Molecules

Objective: The objective of this study was to analyze whether inhibitory and activating killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I alleles defined by their KIR binding motifs are associated with multiple sclerosis (MS) susceptibility or severity. Method: We performed a population-based case–control study in 321 patients with clinically isolated syndrome (CIS) and clinically definite MS (CDMS) and 156 healthy blood donors (HD). Inhibitory and activating KIRs and HLA class I alleles were genotyped using polymerase chain reaction (PCR) sequence-specific primers. Allelic frequencies were correlated with prevalence, age of onset, disability and disease duration of CIS and CDMS. Results: The frequency of the inhibitory KIR2DL3 gene was significantly reduced in patients with CIS and CDMS ( p = 3.1 × 10−5). KIR2DL3-dependent risk reduction remained significant after elimination of patients carrying MS-associated DRB1*15, DRB1*03, DRB1*01 alleles. In addition, individuals carrying two copies for KIR2DL2/KIR2DS2 but lacking KIR2DL3 were overrepresented in the CIS/CDMS cohort. However, both genes did not affect disease risk in presence of KIR2DL3. We did not detect any association between the presence or absence of KIR genes with clinical disease parameters. Conclusion: Absence of the inhibitory KIR2DL3 gene is associated with the development of CIS/CDMS. These findings, if confirmed in larger cohorts, suggest that KIR-mediated recognition of HLA class I molecules should be further explored as potential disease mechanism in MS.

scholarly journals Killer-cell immunoglobulin-like receptor genes linkage disequilibrium analysis in population of Vojvodina

Genetika ◽  
2015 ◽  
Vol 47 (2) ◽  
pp. 439-450
Author(s):  
Svetlana Vojvodic ◽  
D. Ademovic-Sazdanic
Keyword(s):  
Linkage Disequilibrium ◽  
Allelic Variation ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Cytolytic Activity ◽  
Genetic Admixture ◽  
Target Cells ◽  
Structural Level ◽  
Kir Genes ◽  
Genotype Frequencies

Killer Immunoglobulin-like Receptors (KIRs) form a group of regulatory molecules that modulate cytolytic activity of natural killer cells and T cells through interaction with specific human leukocyte antigen (HLA) molecules on target cells. KIRs are encoded by the family of 16 homologous genes that vary substantially between haplotypes and display sequence polymorphism with allelic variation that also contributes to diversity within the complex. The aim of the study is to estimate two locus linkage disequilibrium for 16 KIR loci. In this study, we report the evaluation of KIR gene content, allele, haplotype and genotype frequencies in 175 unrelated healthy individuals from Vojvodina who were KIR typed by polymerase chain reaction-sequence specific primers genotyping assay. The linkage disequilibrium (LD) was studied at the structural level (presence or absence of 16 KIR genes). Our results revealed that linkage disequilibrium is present between telomeric gene pairs KIR2DL1~KIR2DL4, KIR2DP1~KIR2DL4, KIR2DP1~KIR3DL1, KIR2DL1~KIR3DL2, KIR2DP1~KIR3DL2, KIR2DL4~KIR3DL1, KIR2DL4~KIR2DS4, KIR2DL4~KIR3DL2 where (r2=1), but positive association between KIR genes, with higher observed than expected haplotype frequencies were observed for KIR3DS1~KIR2DS1 and KIR2DL5~KIR2DS1 pair of genes (r2=0.646) and (r2=0.371), respectively. Thirty-eight different genotypes were identified, where 12% of the individuals have unique genotype, present in only one person. Our results will help to understand the genetic background of the Vojvodina population, in illustrating the population migration events in the northern part of Serbia, in explaining the extensive genetic admixture amongst the different ethnic groups of the region and also in KIR-related disease studies.

scholarly journals Killer immunoglobulin-like receptor (KIR) genes are associated with the risk of episodes of high-level and detectable viremia among HIV controllers

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 546
Author(s):  
Nathalia Beatriz Ramos De Sá ◽  
Karina dos S. Silva ◽  
Marcelo Ribeiro-Alves ◽  
Diogo Gama Caetano ◽  
Fernanda Heloise Côrtes ◽  
...  
Keyword(s):  
Viral Load ◽  
Viral Replication ◽  
Human Leukocyte ◽  
Nucleotide Polymorphisms ◽  
Elite Controllers ◽  
Viral Control ◽  
Kir Genes ◽  
Specific Amplification ◽  
Hiv Controllers ◽  
High Level

Background: HIV controllers (HICs) constitute a heterogeneous group of HIV-1 individuals able to suppress plasma viremia to low or undetectable levels in the absence of antiretroviral therapy. Host genetic factors may be involved in the sustained control of viral replication observed. We investigated the distribution and the potential impact of human leukocyte antigens (HLA)-B and -C alleles, killer immunoglobulin-like receptor (KIR) genes, single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8 and IL-1β inflammasome genes, and CCR5Δ32 mutation on the viral control among HICs. Methods: In total, 28 HICs were categorized as persistent elite controllers (PECs, n = 7), ebbing elite controllers (EECs, n = 7), and viremic controllers (VCs, n = 14) according to the level of natural suppression of viremia. HLA alleles were assigned by sequencing-based typing, KIR alleles by polymerase chain reaction (PCR) sequence-specific amplification, SNPs by real-time PCR, and the CCR5Δ32 mutation by PCR. Results: Significant differences were observed in the pairwise comparisons of protective HLA-B alleles, KIR Bx genotype, KIR2DL3 + C1 pair, KIR2DL5, and KIR2DS5 allelic carrier frequencies among the HIC groups. Multivariate models showed that HICs without the KIR2DL3 allele or without KIR2DL3 + C1/C2 pair, with the HLA-C*08 allele or with the NLRP3 rs10754558-G SNP had a higher mean hazard of a viral load above 2,000 copies/mL, while a lower mean hazard of this event was observed for HICs with KIR2DL5, KIR2DS1, KIR2DS5, and KIR3DS1 alleles. Moreover, HICs with the KIR2DS5 allele had less risk of undergoing viral load (VL) blips within the same normalized period than those participants without this allele, while HICs without the KIR2DL3 allele had a mean higher risk of experiencing VL blips. Conclusions: These results indicate that innate immune mechanisms may play an essential role in modulating the sustained control of viral replication in HICs.

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