CD4/CD8 Ratio and CD4 Nadir Predict Mortality Following Noncommunicable Disease Diagnosis in Adults Living with HIV

Castilho, Jessica L; Turner, Megan; Shepherd, Bryan E.; Koethe, John R.; Furukawa, Sally S; Bofill, Carmen; Raffanti, Stephen

doi:10.1089/aid.2019.0064

Cited by 24 publications

(22 citation statements)

References 45 publications

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“…Furthermore, our study found that patients whose CD4/CD8 ratio failed to recover to 0.7 may have poor immune function, leading to a higher risk of CKD. These findings have significant implications for the relationship between CD4/CD8 ratio and NCDs in HIV patients, and are an important complement to previous studies (Castilho et al, 2019;Gojak et al, 2019). In addition, we found that the median CD4 cell count in the NNRTI-based group was lower than that in PI-based or INSTI-based groups when CD4/CD8 ratio recovered, however, the incidence of CKD in NNRTI-based group was the lowest (Supplementary Table 3), indicating that although CD4 cell count of some participants did not return to normal level, the risk of CKD could be partially reduced as long as the CD4/CD8 ratio was restored.…”

Section: Discussionsupporting

confidence: 71%

“…Similarly, another study in Italy indicated that only 29% of HIV patients treated with ART who achieved viral suppression reached a CD4/CD8 ratio ≥1.0 ( Mussini et al, 2015 ). Some previous studies have shown that the CD4/CD8 ratio is independently associated with mortality and morbidity of immune dysfunction, and metabolic syndrome ( Sigel et al, 2017 ; Trickey et al, 2017 ; Han et al, 2018 ; Castilho et al, 2019 ; Gojak et al, 2019 ). Therefore, the CD4/CD8 ratio has been considered as an emerging biomarker for HIV-related diseases in recent years ( Serrano-Villar and Deeks, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Association Between CD4/CD8 Ratio Recovery and Chronic Kidney Disease Among Human Immunodeficiency Virus-Infected Patients Receiving Antiretroviral Therapy: A 17-Year Observational Cohort Study

Qin

Wen

et al. 2022

Front. Microbiol.

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Background:CD4/CD8 ratio is considered as an emerging biomarker for human immunodeficiency virus (HIV)-related diseases. However, the relationship of CD4/CD8 ratio recovery and chronic kidney disease (CKD), and whether cumulative antiretroviral therapy (ART) is effective in the CD4/CD8 ratio recovery and in reducing CKD incidence among HIV patients remain unclear.MethodsA 17-year observational cohort study was conducted on all HIV-infected patients receiving ART in Guangxi, China. Kaplan–Meier analysis was used to investigate the cumulative CKD incidence. Cox regression and propensity score matching (PSM) were used to evaluate the association between CD4/CD8 ratio recovery and CKD incidence, and the effect of ART regimens on CD4/CD8 ratio recovery and CKD incidence.ResultsA total of 59,268 eligible individuals contributing 285,143 person-years of follow-up, with an overall CKD incidence of 9.65%. After ART, patients who developed CKD showed higher mortality than those with normal kidney function (12.48 vs. 7.57%, p < 0.001). Patients whose CD4/CD8 ratio did not recover to 0.7 had a higher CKD incidence than the patients who recovered (aHR = 2.84, 95% CI 2.63–3.07), similar to the PSM analysis (aHR = 3.13, 95% CI 2.85–3.45). Compared with the PI-based and INSTI-based regimens, NNRTI-based regimen had a better CD4/CD8 ratio recovery rate (27.04, 16.16, and 29.66%, respectively) and a lower CKD incidence (17.43, 16.16, and 7.31%, respectively).ConclusionThis large-scale real-world setting provide new evidence that the CD4/CD8 ratio recovery is associated with lower CKD incidence in HIV-infected patients receiving ART. NNRTI-based is a better choice for CD4/CD8 ratio recovery and reducing the risk of CKD.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Association Between CD4/CD8 Ratio Recovery and Chronic Kidney Disease Among Human Immunodeficiency Virus-Infected Patients Receiving Antiretroviral Therapy: A 17-Year Observational Cohort Study

Qin

Wen

et al. 2022

Front. Microbiol.

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“…However, a persistent low ratio has been described in certain patients despite ART and is thought to be associated with immunological abnormalities. Previous studies have suggested that the CD4/CD8 ratio is a valuable marker of ageing, immunosenescence and even mortality [ 40 , 41 ]. We explored the association between activation and exhaustion expression markers on both CD4+ and CD8+ T cells, and found that they strongly and inversely correlated with CD4/CD8 ratio in our YWVH population.…”

Section: Discussionmentioning

confidence: 99%

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain

et al. 2021

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Introduction: Immune abnormalities have been described among youth with vertically acquired HIV (YWVH) despite antiretroviral treatment (ART). The CD4/CD8 ratio could be a useful prognostic marker. We assess immune activation and senescence in a cohort of YWVH in comparison to youth without vertically acquired HIV. Methods: YWVH under suppressive ART were included and compared to a group of HIV-negative donors (HD) matched by age and sex, from September 2019 to September 2020. Subset distribution and expression of activation, maturation, senescence and exhaustion markers on T and NK cells were studied on peripheral blood mononuclear cells by multiparametric flow cytometry. Results: Thirty-two YWVH (median age: 24.4 years (interquartile range: 22.5 to 28.3 years)) were included. Among YWVH, CD4-and CD8-T cells showed high levels of activation (HLA-DR/CD38), IL-7 receptor expression (CD127) and exhaustion (TIM-3). Regarding NK cells, YWVH showed increased levels of activation and exhaustion markers compared to HD. Strong inverted correlations were observed between T-cell activation (HLA-DR/CD38), senescence (CD57) and exhaustion (TIGIT, PD-1) levels with the CD4/CD8 ratio among YWVH. HLA-DR, CD69, NKG2D and NKG2A expression levels on NK cells also correlated with the CD4/CD8 ratio. Age at ART initiation was directly associated with higher frequency of CD16 high NK-cell subsets, exhaustion T-cell levels (CD57, TIM3) and NK cells activation levels. Conclusions: Immunological changes associated with vertically acquired HIV, characterized by increased activation and exhaustion levels in innate and adaptive immune components, are only partially restored by ART. The CD4/CD8 ratio can be a useful marker of disease progression for routine clinical practice.

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“…A low CD4 + /CD8 + T-cell ratio has been shown to be an immune risk phenotype related to chronic inflammation, persistent immune dysfunction and immune senescence ( Wikby et al, 2005 ). In some investigations, the CD4 + /CD8 + T-cell ratio was described as a significant marker for prognostic prediction in HIV/AIDS patients ( Castilho et al, 2019 ; Gojak et al, 2019 ; F; Li F. et al, 2019 ). Notably, in our study, the trend found for CD8 + T cells was opposite that found for cytotoxic T cells (cytokine-produced CD8 + T cells) in the network score comparisons.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Long Non-coding RNA KCNQ1OT1 Network in Colorectal Cancer Immunity

Liu

et al. 2021

Front. Genet.

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Over the past few decades, researchers have become aware of the importance of non-coding RNA, which makes up the vast majority of the transcriptome. Long non-coding RNAs (lncRNAs) in turn constitute the largest fraction of non-coding transcripts. Increasing evidence has been found for the crucial roles of lncRNAs in both tissue homeostasis and development, and for their functional contributions to and regulation of the development and progression of various human diseases such as cancers. However, so far, only few findings with regards to functional lncRNAs in cancers have been translated into clinical applications. Based on multiple factors such as binding affinity of miRNAs to their lncRNA sponges, we analyzed the competitive endogenous RNA (ceRNA) network for the colorectal cancer RNA-seq datasets from The Cancer Genome Atlas (TCGA). After performing the ceRNA network construction and survival analysis, the lncRNA KCNQ1OT1 was found to be significantly upregulated in colorectal cancer tissues and associated with the survival of patients. A KCNQ1OT1-related lncRNA-miRNA-mRNA ceRNA network was constructed. A gene set variation analysis (GSVA) indicated that the expression of the KCNQ1OT1 ceRNA network in colorectal cancer tissues and normal tissues were significantly different, not only in the TCGA-COAD dataset but also in three other GEO datasets used as validation. By predicting comprehensive immune cell subsets from gene expression data, in samples grouped by differential expression levels of the KCNQ1OT1 ceRNA network in a cohort of patients, we found that CD4+, CD8+, and cytotoxic T cells and 14 other immune cell subsets were at different levels in the high- and low-KCNQ1OT1 ceRNA network score groups. These results indicated that the KCNQ1OT1 ceRNA network could be involved in the regulation of the tumor microenvironment, which would provide the rationale to further exploit KCNQ1OT1 as a possible functional contributor to and therapeutic target for colorectal cancer.

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CD4/CD8 Ratio and CD4 Nadir Predict Mortality Following Noncommunicable Disease Diagnosis in Adults Living with HIV

Cited by 24 publications

References 45 publications

Association Between CD4/CD8 Ratio Recovery and Chronic Kidney Disease Among Human Immunodeficiency Virus-Infected Patients Receiving Antiretroviral Therapy: A 17-Year Observational Cohort Study

Association Between CD4/CD8 Ratio Recovery and Chronic Kidney Disease Among Human Immunodeficiency Virus-Infected Patients Receiving Antiretroviral Therapy: A 17-Year Observational Cohort Study

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain

Regulation of Long Non-coding RNA KCNQ1OT1 Network in Colorectal Cancer Immunity

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