Role of CD4/CD8 ratio on the incidence of tuberculosis in HIV-infected patients on antiretroviral therapy followed up for more than a decade

Wolday, Dawit; Kebede, Yazezew; Legesse, Dorsisa; Siraj, Dawd; McBride, Joseph A.; Kirsch, Mitchell J.; Striker, Rob

doi:10.1371/journal.pone.0233049

Cited by 17 publications

(17 citation statements)

References 45 publications

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“…The cohort was enrolled at Hayat General Hospital’s ART Clinic in Addis Ababa, Ethiopia, which delivers HIV treatment and care [ 40 ]. The cohort consists of adult patients followed between 2001 and 2017.…”

Section: Methodsmentioning

confidence: 99%

“…Baseline CD4+ T-cell counts were built in to two categories whether normalized (≥500) or not normalized (<500) cells/μL, the CD8 cell counts in three categories (<500, between 500 and 1000, and >1000 cells/μL), and the CD4/CD8 ratio in two categories (<0.30 and ≥0.30). The cut-offs were chosen based on previous reports showing association of the biomarkers with AIDS-related events [ 31 , 32 , 40 ].…”

Section: Methodsmentioning

confidence: 99%

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Immune recovery in HIV-1 infected patients with sustained viral suppression under long-term antiretroviral therapy in Ethiopia

Wolday

Legesse²,

Kebede

et al. 2020

PLoS ONE

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Background There is very little data on long-term immune recovery responses in patients on suppressive antiretroviral therapy (ART) in the setting of sub-Saharan Africa (SSA). Thus, we sought to determine CD4+ T-cell, CD8+ T-cell and CD4/CD8 ratio responses in a cohort of HIV infected individuals on sustained suppressive ART followed up for more than a decade. Methods The cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 14 years. Trends in median CD4+ T-cells, CD8+ T-cells and CD4/CD8 ratio were reviewed retrospectively. Poisson regression models were used to identify factors associated with achieving normalized T-cell biomarkers. Kaplan-Meier curves were used to estimate the probability of attaining normalized counts while on suppressive ART. Results A total of 227 patients with a median duration of follow-up on ART of 12 (IQR: 10.5–13.0) years were included. CD4 cell count increased from baseline median of 138 cells (IQR: 70–202) to 555 cells (IQR: 417–830). CD4 cell increased continuously up until 5 years, after which it plateaued up until 14 years of follow up. Only 69.6% normalized their CD4 cell count within a median of 6.5 (IQR: 3.0–10.5) years. In addition, only 15.9% of the cohort were able to achieve the median reference CD4+ T-cell threshold count in Ethiopians (≈760 cells/μL). CD8+ T-cell counts increased initially until year 1, after which continuous decrease was ascertained. CD4/CD8 ratio trend revealed continuous increase throughout the course of ART, and increased from a median baseline of 0.14 (IQR: 0.09–0.22) to a median of 0.70 (IQR: 0.42–0.95). However, only 12.3% normalized their ratio (≥ 1.0) after a median of 11.5 years. In addition, only 8.8% of the cohort were able to achieve the median reference ratio of healthy Ethiopians. Conclusion Determination of both CD4+ and CD8+ T-cells, along with CD4/CD8 ratio is highly relevant in long-term follow-up of patients to assess immune recovery. Monitoring ratio levels may serve as a better biomarker risk for disease progression among patients on long-term ART. In addition, the findings emphasize the relevance of initiation of ART at the early stage of HIV-1 infection.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Immune recovery in HIV-1 infected patients with sustained viral suppression under long-term antiretroviral therapy in Ethiopia

Wolday

Legesse²,

Kebede

et al. 2020

PLoS ONE

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“…Ki-67 is an early marker of intracellular proliferation, while HLA-DR expression appears later in this process [21,22]. Some studies have indicated that HLA-DR and Ki-67 can be used as biomarkers of infection in TB patients [23].…”

Section: Discussionmentioning

confidence: 99%

Immune Dysfunction of T Lymphocytes may be a Risk Factor for Pleurisy Tuberculoma

Gao¹,

Yang²,

Ji³

et al. 2021

Preprint

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Background: Pleurisy tuberculoma (PTM) is a benign proliferative disease that occurs most commonly after effective treatment of tuberculous pleurisy. In this study, we investigated the risk factors for PTM. Methods: The data of 56 consecutive tuberculoma patients treated at the Nanjing Thoracic Hospital and the Second Hospital between March 2013, and April 2020, were extracted from the hospital database and reviewed retrospectively. Sixty patients treated effectively for tuberculous pleurisy without PTM were included as the control group as most cases of PTM have a history of tuberculous pleurisy. We analyzed the clinical characteristics, laboratory examination results, and imaging features to identify potential risk factors for PTM.Results: The mean age of the PTM patients was 29.04 ± 6.95 years, with no difference between males and females. The onset of PTM was 4.29 ± 2.34 months from the diagnosis of tuberculous pleurisy. The PTM lesions were more commonly located in the lower lobes with no difference in the left and right lung distribution. There were no significant differences in the presenting symptoms and underlying disease of the patients in the PTM and control groups. Pleural thickening was more common in the PTM group (44.64% vs. 23.33% respectively, P = 0.015) and ADA activity was higher (48.32± 19.19 vs. 44.79± 24.57) compared with the control group. There were no significant differences between the groups in terms of the absolute numbers of CD4 + and CD8+ T lymphocyte cells or the CD4+/CD8+ T cell ratio (P > 0.05 ). Expression of the activation marker Ki-67 on CD4+ and CD8+ T cells was significantly increased in the PTM group compared with the control group (P < 0.05).Conclusions: Our results indicate that dysregulation of T lymphocytes may be a potential risk factor for PTM.

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“…The CD4:CD8 ratios de ned in ICM and CCM showed a balance in CD4 + and CD8 + T-cells, whereas in MCM a skew towards the CD8 population was found, in line with the previous report from Zitsman et al 14 , whereas the populations in RM were more biased towards CD4. A low CD4:CD8 ratio has been found to be a predictor TB in HIV patients 15 so as MCM do have the lowest CD4:CD8 ratio, this could be a contributing risk factor in their susceptibility to TB.…”

Section: Cd8 + T-cells and Cd16mentioning

confidence: 99%

Differences in Host Immune Populations Between Rhesus Macaques and Cynomolgus Macaque Subspecies, in Relation to Susceptibility to Mycobacterium Tuberculosis Infection.

Sibley

Daykin-Pont

Sarfas

et al. 2021

Preprint

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Rhesus (Macaca mulatta) and cynomolgus (Macaca fasicularis) macaques of distinct genetic origin are understood to vary in susceptibility to Mycobacterium tuberculosis, and therefore differences in their immune systems may account for the differences in disease control. Monocyte:lymphocyte (M:L) ratio has been identified as a risk factor for M. tuberculosis infection and is known to vary between macaque species. We aimed to characterise the constituent monocyte and lymphocyte populations between macaque species, and profile other major immune cell subsets including: CD4+ and CD8+ T-cells, NK-cells, B-cells, monocyte subsets and myeloid dendritic cells. We found immune cell subsets to vary significantly between macaque species. Frequencies of CD4+ and CD8+ T-cells and the CD4:CD8 ratio showed significant separation between species, while myeloid dendritic cells best associated macaque populations by M. tuberculosis susceptibility. A more comprehensive understanding of the immune parameters between macaque species may contribute to the identification of new biomarkers and correlates of protection.

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Role of CD4/CD8 ratio on the incidence of tuberculosis in HIV-infected patients on antiretroviral therapy followed up for more than a decade

Cited by 17 publications

References 45 publications

Immune recovery in HIV-1 infected patients with sustained viral suppression under long-term antiretroviral therapy in Ethiopia

Immune recovery in HIV-1 infected patients with sustained viral suppression under long-term antiretroviral therapy in Ethiopia

Immune Dysfunction of T Lymphocytes may be a Risk Factor for Pleurisy Tuberculoma

Differences in Host Immune Populations Between Rhesus Macaques and Cynomolgus Macaque Subspecies, in Relation to Susceptibility to Mycobacterium Tuberculosis Infection.

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