Characterization of Natural Killer Cells in HIV Patients Beginning Therapy with a High Burden of Cytomegalovirus

Ariyanto, Ibnu; Estiasari, Riwanti; Edwar, Lukman; Makwana, Nandini; Lee, Silvia; Price, Patricia

doi:10.1080/08820139.2018.1538236

Cited by 8 publications

(15 citation statements)

References 21 publications

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“…Levels of antibody reactive with CMV lysate increased on ART and were markedly higher than in healthy controls. These findings match those reported with the original JakCCANDO cohort (n = 82) [ 14 , 17 ]. As 52% of the original JakCCANDO cohort were CMV DNA+ at V0, we selected 20 HIV patients with and 20 without CMV DNA for this study.…”

Section: Resultssupporting

confidence: 90%

“…Levels of CMV-reactive antibodies were determined relative to a standard plasma pool assigned a value of 1000 arbitrary units (AU). The protocol provides accurate quantitation in the high range [ 17 ]. CMV DNA was detected in buffy coats by qPCR using primer and probe sequences targeting the UL54 gene as described previously [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…CMV DNA was detected in buffy coats by qPCR using primer and probe sequences targeting the UL54 gene as described previously [ 14 ]. CRP and sIFNRα/β levels in plasma were quantitated using commercial ELISA reagents [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

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Which NK cell populations mark the high burden of CMV present in all HIV patients beginning ART in Indonesia?

et al. 2022

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Background Cytomegalovirus (CMV) has been linked with cardiovascular disease (CVD) in populations where some individuals are seronegative. However, effects of CMV are unclear in HIV patients who all have high levels of CMV antibodies. Other metrics of their CMV burden are needed. Amongst transplant recipients, CMV drives the expansion of NK cell populations expressing NKG2C and/or LIR1 and lacking FcRγ. Methods Indonesian HIV patients (n = 40) were tested before ART and after 6 months, with healthy local controls (n = 20). All patients had high CMV antibody titres. 52% started therapy with CMV DNA detectable by qPCR, providing a crude measure of CMV burden. Proportions of CD56Hi or CD56Lo NK cells expressing FcRγ, NKG2C or LIR1 were determined flow cytometrically. CVD was predicted using carotid intimal media thickness (cIMT). Values were correlated with levels of CMV antibodies on ART. Results Patients had low proportions of CD56Lo and more CD56Hi NK cells. However proportions of FcRγ− NK cells were lowest in patients with CMV DNA, and cIMT values related inversely with FcRγ− NK cells in these patients. Percentages of NKG2C+CD56Lo NK cells were similar in patients and controls, but rose in patients with CMV DNA. Proportions of NKG2C+ CD56Hi NK cells correlated with levels of CMV antibodies in CMV DNA-negative patients. Conclusions We show that the very high burdens of CMV in this population confound systems developed to study effects of CMV in other populations. FcRγ− NK cells may be depleted by very high CMV burdens, but NKG2C and antibody levels may be informative in patients on ART.

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Section: Resultssupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

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Which NK cell populations mark the high burden of CMV present in all HIV patients beginning ART in Indonesia?

et al. 2022

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“…The high proportion of patients beginning ART with detectable CMV DNA is pertinent to this. 18 Earlier studies 9,15,17 suggest complicated associations between RAC, inflammation and markers of lipid metabolism. Further investigations into the apparently protective role of CMV appear to be warranted, and should address both eyes as the underlying mechanisms may be different.…”

Section: Discussionmentioning

confidence: 98%

Factors Affecting the Health of Retinal Vessels in Human Immunodeficiency Virus Patients Beginning Anti-Retroviral Therapy

Edwar

Karim

Wijaya

et al. 2019

AIDS Research and Human Retroviruses

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HIV patients responding to antiretroviral therapy (ART) have a high burden of cytomegalovirus (CMV) and display accelerated cardiovascular change assessed systemically. We assessed the effects of HIV, ART and CMV on retinal artery calibers (RAC), as a non-invasive measure of vasculopathy in HIV patients beginning ART. We analysed 79 HIV patients beginning ART in Jakarta, Indonesia, with a median (range) age of 31 (19-48) years. RAC was assessed using Image J software from fundus photos of both eyes, before ART (V0) and after 3-12 months (V3-V12). CMV DNA and antibodies were assessed. Systemic vascular pathology was assessed by carotid intima media thickness (cIMT). Multivariable models assessed which variables best predicted RAC values at V12. HIV patients had narrower retinal arteries and higher levels of CMV antibodies than healthy controls. RAC decreased over 12 months of ART (p < .0001). Right RAC correlated with CMV IE-1 antibody, while the left RAC at V3 correlated with cIMT. Multivariable models linked RAC at V12 with detectable HIV RNA at V12 and declared use of alcoholic drinks, while a smoking habit was protective. Decreases in RAC in HIV patients responding to ART suggest progressive microvascular change distinct from changes assessed in large vessels. Correlations with CMV IE-1 antibodies suggest the decline in RAC may be accelerated by frequent reactivations of CMV. This may be a feature of severe HIV disease before ART, confirmed by associations with high baseline HIV RNA in multivariable models. Links with alcohol consumption and smoking testify to a complex pattern of modifiable risk factors.

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“…Its expression in HIV patients is increased by their burden of CMV and reduced by a deletion mutation, with complex patterns seen in heterozygotes. 18 Here we address variations in genes encoding inflammatory mediators and NK receptors, and assess which can affect RAC in each eye in HIV patients beginning ART. We align the data with the effects of genotype on CD4 T-cell counts and control of HIV replication.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1A May Illuminate Differential Effects of the Retinal Artery Caliber in HIV Patients

Edwar

Ariyanto

Tanudjaja

et al. 2021

Mol Cell Biomed Sci

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Background: Retinal artery caliber (RAC) is narrower in human immunodeficiency virus (HIV)-infected patients beginning antiretroviral therapy (ART). We aimed to assess associations between variations in genes encoding inflammatory mediators and natural killer receptors and retinal artery caliber (RAC) in HIV patients beginning ART.Materials and Methods: Seventy-nine HIV positive patients beginning ART with less than 200 cluster of differentiation (CD) 4 T-cells/μL were recruited. Examinations were performed before ART (V0) and at months 3, 6 and 12 (V3, V6, V12). The study was approved by ethics committees and informed consent was obtained from each subject.Results: Right and left RAC of the HIV patients were narrower than healthy controls (p=0.016 for right RAC) and narrowed further on ART, but demographic associations with the right and left RAC were not identical. Here we show that polymorphisms in genes encoding NK receptors or TNF activity had no significant impact, but right RAC was associated with carriage of allele 2 at IL1A+4845 (p=0.037 after 12 months on ART).Conclusion: Overall the paradoxical reduction in the RAC in HIV patients responding to ART was not modified by genotypes known to affect NK cell function or TNF responses, but IL1A genotype may modify the decline in the right RAC.Keywords: anti-retroviral therapy, CMV, HIV, IL1A, retinal artery caliber

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Characterization of Natural Killer Cells in HIV Patients Beginning Therapy with a High Burden of Cytomegalovirus

Cited by 8 publications

References 21 publications

Which NK cell populations mark the high burden of CMV present in all HIV patients beginning ART in Indonesia?

Which NK cell populations mark the high burden of CMV present in all HIV patients beginning ART in Indonesia?

Factors Affecting the Health of Retinal Vessels in Human Immunodeficiency Virus Patients Beginning Anti-Retroviral Therapy

Interleukin-1A May Illuminate Differential Effects of the Retinal Artery Caliber in HIV Patients

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