Immune Dysfunction in HIV: A Possible Role for Pro- and Anti-Inflammatory Cytokines in HIV Staging

HIV infection is a chronic infection that almost inevitably progresses to AIDS. The infection is characterized by the deterioration in the immune function leading to opportunistic infections and malignancies. Additionally, there is an associated immune dysfunction characterized by a persistent inflammatory state and unhealthy elaboration of both pro- and anti-inflammatory cytokines. The CD4+ T cell count has been used as a surrogate for the level of immune dysfunction that exists in patients with HIV infection. Eighty-eight (88) patients with HIV infection, forty-four (44) of whom were treatment naïve patients and forty-four (44) who were treatment-experienced patients, were recruited. The serum concentrations of cytokines IL-6 and IL-10 were carried out using R&D human Quantikine ELISA kits, while patients’ CD4+ T cell counts were evaluated using the Partec easy count kit. The serum IL-6 and IL-10 concentrations were significantly higher among the AR-naïve participants compared to the ART-experienced group. Additionally, the IL-6 and IL-10 concentrations were higher in patients with lower CD4+ T cell count compared to those with higher cell counts though this was not statistically significant. Also, both IL-6 and IL-10 concentrations were higher in patients with higher WHO clinical staging of disease, significantly so for IL-6.

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Prospective study of opportunistic infections among HIV infected patients in VSS Institute of Medical Science and Research, Burla, Sambalpur, Odisha, India

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20181980 ◽

2018 ◽

Vol 5 (3) ◽

pp. 566

Author(s):

P. K. Bariha ◽

M. K. Mohapatra ◽

B. K. Kullu ◽

P. C. Karua ◽

S. B. Biswal ◽

...

Keyword(s):

T Cell ◽

Prospective Study ◽

Cell Count ◽

Opportunistic Infections ◽

Oral Candidiasis ◽

Medical Science ◽

Cd4 T Cell ◽

Female Ratio ◽

Cell Counts ◽

Cd4 T Cell Count

Background: HIV destroys the CD4+T cells progressively thus making the HIV infected persons susceptible to a number of opportunistic infections (OIs).Methods: The study was conducted in the Medicine Department and ART Centre, VIMSAR. It is a prospective study from July 2016 to September 2017.Results: 86 patients register, detail history, clinical examination and investigation were done and then the data is complying in detail. Most of the patients were male (72%) male female ratio is 2.6:1. The majority of patients presented with fever, weight loss and anorexia seen in more than 73% of the study population.Conclusions: (42%) cases belonged to the CD4+T cell count range of 101-200/µl with aCD4+T cell count of 183/µl, so there is increased chance of hospitalization in patients having CD4+T cell count below 200/µl. The most common OI was tuberculosis (51%) with pleural effusion as its commonest manifestation. The second most common OI was candidiasis (43%) with most cases suffering from oral candidiasis was seen to occur at higher CD4+T cell counts than tuberculosis.

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Factors Associated with Immune Discordant Responses in Treated HIV-infected Omani Patients

The Open AIDS Journal ◽

10.2174/1874613601913010025 ◽

2019 ◽

Vol 13 (1) ◽

pp. 25-30

Author(s):

Zied Gaifer Ali ◽

Mohamed-Rachid Boulassel

Keyword(s):

T Cell ◽

Cell Count ◽

Opportunistic Infections ◽

Significant Proportion ◽

Hiv Viral Load ◽

Viral Control ◽

Logistic Regression Models ◽

Factors Associated ◽

Cell Counts ◽

The Impact

Background: Despite sustained viral control by antiretroviral therapy (ART), some HIV-infected patients do not recover normal CD4+ T cell counts. This Discordant Immune Response (DIR) increases the risk of opportunistic infections. Objective: To evaluate the factors associated with DIR in HIV-infected Omani patients attending public sector clinics. Methods: All HIV-infected patients receiving ART with regular follow-up visits were eligible for this study. The DIR group comprised patients on ART for at least two years with plasma HIV viral load < 50 copies/mL and helper CD4+ T cell counts below 350 cells/μl. The Concordant Immune Responses (CIR) group was similar to DIR but with CD4+ T cell counts above 350 cells/μl. Univariate and multivariate analyses using logistic regression models were used to assess the impact of demographic characteristics, clinical, immunological and virological parameters, type of ART regimens, tuberculosis and other opportunistic co-infections on DIR. Results: Among 153 enrolled participants, 28 and 76 patients were identified as having DIR and CIR, respectively. The multivariate analysis revealed that the only factors independently associated with DIR after adjustment were age (odds ratio [OR] 1.13; 95% confidence interval [CI] 1.04-1.23), baseline CD4+ T cell count (OR: 0.98; CI: 0.97-0.99) and baseline CD56+ cell count (OR: 0.97; CI: 0.96-0.99). Conclusion: Collectively, these findings suggest that a significant proportion of HIV-infected Omani patients develop DIR totaling 27%, and efforts should be made to improve early identification of these patients who tend to experience poor clinical outcomes.

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Immune dysfunction following COVID-19, especially in severe patients

Scientific Reports ◽

10.1038/s41598-020-72718-9 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Cong-Ying Song ◽

Jia Xu ◽

Jian-Qin He ◽

Yuan-Qiang Lu

Keyword(s):

Risk Factors ◽

T Cell ◽

Blood Cell ◽

Cell Count ◽

Nk Cell ◽

Multivariate Logistic Regression Analysis ◽

Immune Dysfunction ◽

Early Screening ◽

Cell Counts ◽

D Dimer

Abstract The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify the risk factors associated with its progression. Data of confirmed SARS-CoV-2-infected patients and healthy participants were collected. Thirty-seven healthy people and 79 confirmed patients, which include 48 severe patients and 31 mild patients, were recruited. COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines). Also, they were found to have increased levels of white blood cell, neutrophil count, and D-dimer in severe cases. Moreover, lymphocyte, CD4+ T cell, CD8+ T cell, NK cell, and B cell counts were lower in the severe group. Multivariate logistic regression analysis showed that CD4+ cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Both CT score and clinical pulmonary infection score (CPIS) were associated with disease severity. The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases.

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The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients

Current HIV Research ◽

10.2174/1570162x18666200712174642 ◽

2020 ◽

Vol 18 (5) ◽

pp. 354-361

Author(s):

Gülay Okay ◽

Meliha Meric Koc ◽

Eray Metin Guler ◽

Ayşegül Yabaci ◽

Abdürrahim Kocyigit ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

Cell Count ◽

Cd4 T Cell ◽

Positive Correlation ◽

Hiv Rna ◽

Tnf Α ◽

Cytokine Levels ◽

Ifn Γ ◽

Cd4 T Cell Count

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

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Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia

BMC Infectious Diseases ◽

10.1186/s12879-021-06124-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fan Jin ◽

Jing Xie ◽

Huan-ling Wang

Keyword(s):

T Cell ◽

Cell Count ◽

Lymphocyte Subsets ◽

Nk Cell ◽

Cd8 T Cell ◽

Pneumocystis Pneumonia ◽

Lymphocyte Subset ◽

Cd4 T Cell ◽

Cell Counts ◽

Hiv Negative

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

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CD4+ T cell count, HIV-1 viral loads and demographic variables of newly identified patients with HIV infection in Wuhan, China

Journal of Medical Virology ◽

10.1002/jmv.23627 ◽

2013 ◽

Vol 85 (10) ◽

pp. 1687-1691 ◽

Cited By ~ 5

Author(s):

Man-Qing Liu ◽

Li Tang ◽

Wen-Hua Kong ◽

Ze-Rong Zhu ◽

Jin-Song Peng ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

Cell Count ◽

Demographic Variables ◽

Cd4 T Cell ◽

Viral Loads ◽

Hiv 1 ◽

Cd4 T Cell Count

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PIMATM point-of-care testing for CD4 counts in predicting antiretroviral initiation in HIV-infected individuals in KwaZulu-Natal, Durban, South Africa

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v17i1.444 ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Mandisa Skhosana ◽

Shabashini Reddy ◽

Tarylee Reddy ◽

Siphelele Ntoyanto ◽

Elizabeth Spooner ◽

...

Keyword(s):

South Africa ◽

T Cells ◽

T Cell ◽

Antiretroviral Therapy ◽

Cell Count ◽

Point Of Care ◽

Cd4 T Cell ◽

Cell Counts ◽

Kwazulu Natal ◽

Cd4 T Cell Count

Introduction: Limited information is available on the usefulness of the PIMATM analyser in predicting antiretroviral treatment eligibility and outcome in a primary healthcare clinic setting in disadvantaged communities in KwaZulu-Natal, South Africa.Materials and methods: The study was conducted under the eThekwini Health Unit, Durban, KwaZulu-Natal. Comparison of the enumeration of CD4+ T-cells in 268 patients using the PIMATM analyser and the predicate National Health Laboratory Services (NHLS) was undertaken during January to July 2013. Bland-Altman analysis to calculate bias and limits of agreement, precision and levels of clinical misclassification at various CD4+ T-cell count thresholds was performed.Results: There was high precision of the PIMATM control bead cartridges with low and normal CD4+ T-cell counts using three different PIMATM analysers (%CV < 5). Under World Health Organization (WHO) guidelines (≤ 500 cells/mm3), the sensitivity of the PIMATM analyser was 94%, specificity 78% and positive predictive value (PPV) 95%. There were 24 (9%) misclassifications, of which 13 were false-negative in whom the mean bias was 149 CD4+ T-cells/mm3. Most (87%) patients returned for their CD4 test result but only 67% (110/164) of those eligible (≤ 350 cells/mm3) were initiated on antiretroviral therapy (ART) with a time to treatment of 49 days (interquartile range [IQR], 42–64 days).Conclusion: There was adequate agreement between PIMATM analyser and predicate NHLS CD4+ T-cell count enumeration (≤ 500 cells/mm3) in adult HIV-positive individuals. The high PPV, sensitivity and acceptable specificity of the PIMATM analyser technology lend it as a reliable tool in predicting eligibility and rapid linkage to care in ART programmes.Keywords: HIV; Point of Care; PIMATM CD4+ T cell counts; antiretroviral therapy; prediction/eligibility; South Africa

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Lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients

10.21203/rs.3.rs-52336/v2 ◽

2020 ◽

Author(s):

Daxian Wu ◽

Xiaoping Wu ◽

Jiansheng Huang ◽

Qunfang Rao ◽

Qi Zhang ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Count ◽

Disease Severity ◽

Lymphocyte Subsets ◽

Nk Cell ◽

Lymphocyte Subset ◽

Multivariate Logistic Regression ◽

Cell Counts ◽

Glutamyl Transpeptidase

Abstract Background: COVID-19 continuously threated public health heavily. Present study aimed to investigate the lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients.Methods: Lymphocyte subsets was classified using flow cytometry with peripheral blood collected from 106 patients.Results: Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent predictors for severe COVID-19. The T cell, CD4+ T cell and B cell counts in severe patients were significantly lower than that in mild patients (p = 0.004, 0.003 and 0.046, respectively). Only the T cell count was gradually decreased with the increase of infiltrated quadrants of lesions in computed tomography (CT) (p = 0.043). The T cell, CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increase of infiltrated area of the maximum lesion in CT (p = 0.002, 0.003, 0.028; respectively). The T cell count, as well as CD4+ T cell, CD8+ T cell, and NK cell counts were gradually decreased with the increased delayed hospitalization (p = 0.003, 0.002, 0.013, and 0.012; respectively). The proportion of T cell was gradually decreased but B cell was gradually increased with the increased delayed hospitalization (p = 0.031 and 0.003, respectively).Conclusion: T cell and CD4+ T cell counts negatively correlated with disease severity, CT manifestation and delayed hospitalization. CD4+ T cell was mainstay of immunity response in COVID-19 patients.

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321. Low Volumetric Bone Density at Proximal Femur in HIV-Infected Men and Its Risk Factors: Comparison with Community-Dwelling Non-Infected Men

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.394 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S170-S170

Author(s):

Jung Ho Kim ◽

Namki Hong ◽

Woon Ji Lee ◽

Hye Seong ◽

Jin young Ahn ◽

...

Keyword(s):

Risk Factors ◽

T Cell ◽

Hiv Infection ◽

Protease Inhibitor ◽

Cell Count ◽

Community Dwelling ◽

Cd4 T Cell ◽

Total Hip ◽

Tertiary Center ◽

Cd4 T Cell Count

Abstract Background Individuals with HIV infection is at increased risk of low area bone mineral density (BMD) and fracture. However, data regarding volumetric BMD (vBMD) of central bone determined by quantitative computed tomography (QCT) which can distinguish the cortical and trabecular bone component are limited. Methods From November 2017 to October 2018, we measured spine and hip vBMD in HIV-infected men aged 30 years or older at the tertiary center. QCT data were compared with 1:2 matched control by age- and body mass index (BMI) sampled from a community-based healthy individual cohort. HIV-specific risk factors for low total hip vBMD as a primary outcome were identified using multivariate linear regression models. Results A total of 83 HIV-infected men and 166 control were analyzed (mean age 47.4 vs. 47.0 year; BMI 23.3 vs. 23.7 kg/m2; P > 0.05). In HIV-infected men, vBMD of trochanter, intertrochanter and total hip was significantly lower than that of non-infected men. (198 ± 31 vs. 213 ± 32; 339 ± 50 vs. 356 ± 47; 280 ± 41 vs. 296 ± 41 mg/cc; all P < 0.05) Association between HIV infection and lower total hip vBMD remained robust (Adjusted β -14.4; P = 0.013) after adjustment for age, diabetes, smoking, and vitamin D status. In HIV cohort, low CD4 T-cell count at initial diagnosis (< 200 vs. ≥200 cells/μL; Adjusted β = −6.7, P = 0.015) and use of protease inhibitor (vs. integrase inhibitor; Adjusted β = −29.9, P = 0.029) were negatively associated with total hip vBMD, after adjustment for age, BMI, and duration of HIV infection, whereas tenofovir disoproxil fumarate use was not. (Adjusted β −12.1, P = 0.280) In HIV-infected men with low tertile total hip vBMD, the levels of β-crosslaps (0.42 ± 0.23 vs. 0.30 ± 0.16 ng/mL; P = 0.012) and osteocalcin (22.10 ± 8.65 vs. 16.57 ± 6.04 ng/mL; P = 0.001) were higher than those with middle-upper tertile total hip vBMD. Conclusion HIV-infected men had lower hip vBMD compared with age- and BMI-matched non-infected men. Low baseline CD4 T-cell count and protease inhibitor use were independent risk factors for lower total hip vBMD. High born turnover was attributable to the negative effect on born health of HIV-infected men. Disclosures All authors: No reported disclosures.

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The combination of CXCL9, CXCL10 and CXCL11 levels during primary HIV infection predicts HIV disease progression

Journal of Translational Medicine ◽

10.1186/s12967-019-02172-3 ◽

2019 ◽

Vol 17 (1) ◽

Author(s):

Xiaowan Yin ◽

Zhuo Wang ◽

Tong Wu ◽

Meichen Ma ◽

Zining Zhang ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

Cell Count ◽

Disease Progression ◽

Risk Score ◽

Point Group ◽

Clinical Information ◽

Hiv Disease ◽

Set Point ◽

Primary Hiv Infection

Abstract Background Chemokines are small chemotactic cytokines involved in inflammation, cell migration, and immune regulation in both physiological and pathological contexts. Here, we investigated the profile of chemokines during primary HIV infection (PHI). Methods Fifty-four participants with blood samples before and during HIV infection and clinical information available were selected from an HIV-negative man who have sex with men (MSM) prospective cohort. Thirty chemokines and 10 cytokines were measured pre- and post-HIV infection in the same individuals using a Bio-Plex Pro™ Human Chemokine Panel. Results Levels of 18 chemokines/cytokines changed significantly during PHI relative to pre-HIV infection levels; 14 were up-regulated and 4 down-regulated. Among them, CXCL9, CXCL10, and CXCL11 were the most prominently raised. Levels of CXCL9 and CXCL10 were much higher in the high-set point group (log viral load (lgVL) ≥ 4.5) than those in the low-set point group (lgVL < 4.5) and levels of CXCL9, CXCL10, and CXCL11 were higher in the low-CD4+ T-cell count group (CD4+ T-cell count ≥ 500). A formula to predict HIV disease progression using a combination panel comprising CXCL9, CXCL10, and CXCL11 was developed, where risk score = 0.007 × CXCL9 + 0.004 × CXCL10 − 0.033 × CXCL11 − 1.724, with risk score values higher than the cutoff threshold (0.5211) indicating more rapid HIV disease progression. Conclusions A panel of plasma CXCL9, CXCL10, and CXCL11 measured during primary HIV-1 infection could predict long-term HIV disease prognosis in an MSM group and has potential as a novel biomarker in the clinic.

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