Increased CD4 : CD8 ratio normalization with implementation of current ART management guidelines

Zhabokritsky, Alice; Szadkowski, Leah; Cooper, Curtis; Loutfy, Mona; Wong, Alexander; McClean, Alison R; Hogg, Robert S.; Walmsley, Sharon

doi:10.1093/jac/dkaa484

Cited by 9 publications

(11 citation statements)

References 20 publications

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“…Features of immunosenescence in HIV‐negative individuals include low CD4/CD8+ T‐cell ratio [ 34 , 35 ]. In most PLWH, ART normalizes CD4/CD8 ratio by increasing the percentage of CD4+ T cells to normal levels [ 28 , 36 , 37 , 38 , 39 ]. However, a persistent low ratio has been described in certain patients despite ART and is thought to be associated with immunological abnormalities.…”

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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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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“…Although studies related to normalization of the CD4/CD8 ratio with early ART initiation have been published [ 20 – 22 ], no differences have been found among the different classes of ART used [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Predictors of subclinical atherosclerosis in HIV

et al. 2023

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Background Cardiovascular disease is a major cause of morbidity and mortality in people with HIV. The detection of subclinical atherosclerosis through vascular ultrasound allows us to identify patients at an increased risk of cardiovascular disease as a primary prevention strategy; this test is not routine. Our objective is to identify predictors of subclinical atherosclerosis in a population with HIV. Methods People with HIV infection were selected for primary prevention and underwent carotid and femoral ultrasound to detect atheromatous plaques. Logistic regression analysis including vascular risk factors was performed to predict the presence of atherosclerosis. Results One hundred eighty-three patients were included, 54% of whom were smokers; the mean duration of HIV infection was 9.52 years, and all patients were undergoing antiretroviral treatment. Subclinical atherosclerosis was present in 62.29% of the patients; 83.32% had plaque in the carotid territory, 57.93% in the femoral territory and 25.6% in both vascular territories. Compared to those without atherosclerosis, patients with atherosclerosis were on average 5.35 years older (53.86 vs. 48.51, p < 0.001) and had a higher prevalence of smoking (63.23% vs. 39.12%, p = 0.020) and a CD4/CD8 ratio below 0.7 (44.23% vs. 29.02%, p = 0.043). A CD4/CD8 ratio lower than 0.3 was always associated with subclinical atherosclerosis (95% confidence interval (CI): 83.9–100%). The inclusion of smoking, the CD4/CD8 ratio and age in the logistic regression analysis led to a diagnostic yield of 72% measured by the area under the receiving operator characteristic (ROC) curve (95% CI: 64–80%). Conclusions Tobacco use, age and a CD4/CD8 ratio below 0.7 allow prediction of the presence of subclinical atherosclerosis in primary prevention. A CD4/CD8 ratio below 0.3 was a diagnostic indicator of atherosclerosis in HIV patients undergoing primary prevention in our sample.

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“…Additionally, RA is a kind of autoimmune disease, and the immune homeostasis and preventing autoimmunity were inseparable from Treg cells. CD4+ T cells regulate the inflammatory environment in RA through various subsets, CD4+/CD8+ is associated with immune dysfunction, an increased CD4+/CD8+ ratio has been implicated in patients with RA, while the development and suppressive activity of Treg cells require the master regulator FOXP3 [ 40 , 41 , 42 ]. In this study, FOXP3 expression was increased and the ratio of CD4+ and CD8+ was decreased by purpurin treatment, which further supported its potential efficacies of against RA.…”

Section: Discussionmentioning

confidence: 99%

The Effective Treatment of Purpurin on Inflammation and Adjuvant-Induced Arthritis

Zeng

Shen

et al. 2023

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Rubia cordifolia L. (Rubiaceae), one of the traditional anti-rheumatic herbal medicines in China, has been used to treat rheumatoid arthritis (RA) since ancient times. Purpurin, an active compound of Rubia cordifolia L., has been identified in previous studies and exerts antibacterial, antigenotoxic, anticancer, and antioxidant effects. However, the efficacy and the underlying mechanism of purpurin to alleviate RA are unclear. In this study, the effect of purpurin on inflammation was investigated using macrophage RAW264.7 inflammatory cells, induced by lipopolysaccharide (LPS), and adjuvant-induced arthritis (AIA) rat was established to explore the effect of purpurin on joint damage and immune disorders; the network pharmacology and molecular docking were integrated to dig out the prospective target. Purpurin showed significantly anti-inflammatory effect by reducing the content of IL-6, TNF-α, and IL-1β and increasing IL-10. Besides, purpurin obviously improved joint injury and hypotoxicity in the liver and spleen and regulated the level of FOXP3 and CD4+/CD8+. Furthermore, purpurin reduced the MMP3 content of AIA rats. Network pharmacology and molecular docking also suggested that MMP3 may be the key target of purpurin against RA. The results of this study strongly indicated that purpurin has a potential effect on anti-RA.

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Increased CD4 : CD8 ratio normalization with implementation of current ART management guidelines

Cited by 9 publications

References 20 publications

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

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

Predictors of subclinical atherosclerosis in HIV

The Effective Treatment of Purpurin on Inflammation and Adjuvant-Induced Arthritis

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