Absolute CD4 Counts Research Articles

S2799 Disseminated Cryptococcosis Masquerading as Large Abdominal Mass Concerning for Pancreatic Malignancy in HIV-Positive Patient

Introduction: Gastrointestinal cryptococcus is a rare occurrence in HIV-positive patients. Symptoms may be nonspecific thus the differential for abdominal masses must remain broad. We report a patient with HIV who presented with abdominal pain and watery diarrhea, found to have a large abdominal mass on computed tomography initially thought to be lymphoma or a primary pancreatic tumor. He underwent endoscopic ultrasound-guided (EUS) biopsy of the mass which was consistent with a cryptococcoma. Case Description/Methods: A 55-year-old male presented with severe, diffuse abdominal pain for one week duration associated with profuse watery, non-bloody diarrhea and intermittent chills. Medical history included HIV for 30 years with poor compliance with antiretroviral regimen, recent pneumocystis pneumonia and previous cryptococcal meningitis. Physical exam revealed an ill appearing, cachectic male with abdominal tenderness. Labs revealed a white blood cell count of 18.5 K/uL (ref: 4.0-10.8 K/uL) with 84% neutrophils (ref: 40-75%), sodium of 132 mmol/L (ref: 135-146 mmol/L) and potassium 2.7 mmol/L (ref: 3.5-5.1 mmol/L). His viral load was 109,385 copies/mL (ref: neg copies/mL) and absolute CD4 count was 56 lymphocytes/uL (ref: 330-1520 lymphocytes/uL). Liver chemistries were unremarkable. Stool studies for regional pathogens, ova and parasites, and clostridium difficile were negative. A CT scan of the abdomen and pelvis revealed ill-defined cystic/necrotic upper abdominal lymphadenopathy with mass effect and possible invasion of the adjacent liver (Figure 1A). The pancreas and caudate lobe of the liver were inseparable from the mass which raised concern for primary pancreatic tumor or lymphoma. He underwent EUS-guided biopsy of the peripancreatic mass (Figure 1B) with pathology consistent with a cryptococcoma (Figure 1C, 1D). He was started on amphotericin B and transitioned to high dose fluconazole due to adverse effects. Repeat imaging revealed significant reduction of the mesenteric lymphadenopathy (Figure 1E). He was discharged in stable condition and remained on fluconazole indefinitely. Discussion: Cryptococcal infection remains the second most common cause of acquired immunodeficiency syndrome related mortality after tuberculosis. The most common sites of cryptococcal infection are the lungs, brain, eyes, or central nervous system; abdominal dissemination is rare. Biopsy via EUS can be useful in diagnosis of cryptococcoma. Early identification and treatment of cryptococcal infections can increase survival rates.Figure 1.: A) CT image showing ill-defined cystic/necrotic upper abdominal lymphadenopathy with mass effect and possible invasion of the adjacent liver B) Endoscopic ultrasound imaging showing peripancreatic mass C) Hematoxylin and Eosin cellblock at 40X magnification showing abundant neutrophils and necrotic debris D) Grocott’s Methenamine Silver stain showing fungal yeast with narrow base budding E) Significant reduction of the mesenteric lymphadenopathy after antifungal therapy initiation.

S2177 Clostridium difficile-Like Diarrhea

Introduction: Clostridium difficile is an important cause of diarrhea in immunosuppressed patients, recent use of antibiotics and in patients presenting from nursing facility. We present a patient with HIV, recently treated with Augmentin and started on a new medication (Juluca) for HIV presenting with watery diarrhea and abdominal pain. Case Description/Methods: 62-year-old woman with HIV infection presented with abdominal pain and watery diarrhea for 2 days. She recently had ureteroscopy and was prescribed Augmentin which she completed about a week ago. She denied any GU complaints. She was started on Juluca (Dolutegravir/ Rilpivirine) for treatment of HIV one day before onset of symptoms. She had diffuse tenderness on abdominal exam and had leukocytosis (23.1k/mcl) with an absolute CD4 count of 568/mcl. On CT scan abdomen she had pancolitis with free fluid. She was found to have Clostridium antigen but without any toxin. On flexible sigmoidoscopy she had lesions shown in the Figure. Erythematous, edematous mucosa and inflamed plaques were seen on ulcerated mucosa with narrowing of sigmoid colon. No pseudomembranes or cytological atypia was seen on histopathology. Specimen culture did not show C. difficile. Discussion: There are multiple causes of inflammatory diarrhea in an immunocompromised host with HIV. Previous infection with C. difficile and recent use of antibiotics increase the risk of C. difficile diarrhea. As per the center of disease control, about a half a million people are infected with C. difficile annually and one in 6 patients will get recurrent infection in 2 to 8 weeks. Our patient presented with multiple risk factors including history of C. difficile, HIV and recent use of antibiotics. The images of sigmoidoscopy were suggestive of pseudomembranous colitis though the tissues without any pathological or microbiological evidence. It highlights the importance of considering other non infectious causes of inflammatory diarrhea like medications. Dolutegravir/ rilpivirine are new class of medications (Integrase inhibitors). In a study by Curtis et al less than 2% of cases had diarrhea but none were severe enough o warrant discontinuation of therapy. Our patient had severe symptoms and required discontinuation of Juluca with regression of his symptoms.Figure 1.: A and B- Images of recto-sigmoid showing pseudomembranes in an edematous, erythematous colon. C,D - Marked narrowing of the sigmoid colon.

Increased percentage of apoptotic and CTLA-4 (CD152) expressing cells in CD4+/CD8+ cells in COVID-19 patients.

Coronavirus infectious disease 2019 (COVID-19) confirmed cases are characterized by T lymphopenia. Total apoptotic and cytotoxic T-lymphocyte antigen-4 (CTLA-4) expressing cells among CD4+/CD8+ cells were analyzed in 24 COVID-19 patients (16 out-patients and 8 in-patients) and 18 healthy volunteers using flow cytometry to detect their possible role in T lymphopenia. Hospitalized patients did not show significant difference compared to non-hospitalized patients. While the percentage and absolute count of CD4+/CD8+ cells were significantly reduced in COVID-19 cases compared to healthy control (P < .05), the proportion of apoptotic and CTLA-4 expressing CD4+/CD8+ cells were significantly up-regulated in COVID-19 patients (P < .05). In addition, apoptotic and CTLA-4+/CD4+ cells were directly related to dyspnea duration, chest CT score, ferritin, and C-reactive protein and inversely correlated with platelet count in COVID-19 patients. While apoptotic and CTLA-4+/CD8+ cells were directly related to lymphocyte count in COVID-19 patients. The apoptotic and CTLA-4+ cells were directly related to each other in CD4+/CD8+ cells (P < .05). White blood cells (WBCs) (×103/L), eosinophils (ratio and count), lymphocyte ratio, neutrophil ratio, neutrophil/lymphocyte ratio, neutrophil/CD4 ratio, neutrophil/CD8 ratio, CD4+ cells ratio, and CTLA-4+ cells percentage), and CD8+ cells (ratio, count, total apoptotic cell, and CD152 + cells) were all found to be significantly altered in association with COVID-19. Total lymphopenia and depletion of CD4+/CD8+ cells are characterizing COVID-19 patients. Increased apoptosis and CTLA-4 expression in CD4+/CD8+ cells in COVID-19 and their correlations with reduced cell count and severity indicators as CRP and ferritin can be used for diagnosis and follow up of the clinical severity. Our current study proposes promising future diagnostic and therapeutic targets.

Rare Case of Persistently Depressed T Lymphocyte Subsets After SARS-CoV-2 Infection

BACKGROUND On rare occasions, viral infections are known to also depress immune cell lines, further worsening clinical outcomes. We describe a patient who presented 3 weeks after recovery from mild COVID-19 disease with clinical features of an atypical pneumonia and was found to have a low CD4+ T-cell count. CASE REPORT An 82-year-old man with a past medical history of coronary artery disease, rheumatoid arthritis, gout, hypertension, and atrial fibrillation presented with a 1-week history of progressively worsening shortness of breath and cough. He was noted to have recovered from mild SARS-CoV-2 infection 3 weeks prior to his current presentation and had been at his baseline level of health following infection. A T cell subset panel was obtained, which revealed an absolute CD3 count of 92 (reference range 840-3060), absolute CD4 count of 52 (reference range 500-1400), absolute CD8 count of 37 (reference range 180-1170), and a normal CD4: CD8 ratio. He was subsequently started on atovaquone for pneumocystis jiroveci pneumonia prophylaxis. CONCLUSIONS This case highlights the need for a high index of suspicion for lymphocyte depletion in older patients with multiple comorbidities who present during or after SARS-CoV-2 infection with atypical symptoms that are suggestive of immunosuppression. In such instances, there should be a low threshold to start prophylactic therapy for possible opportunistic infections.

Clinical predictive value of naïve and memory T cells in advanced NSCLC.

Currently, there is no sensitive prognostic biomarker to screen out benefit patients from the non-benefit population in advanced non-small cell lung cancer patients (aNSCLCs). The 435 aNSCLCs and 278 normal controls (NCs) were recruited. The percentages and absolute counts (AC) of circulating naïve and memory T lymphocytes of CD4+ and CD8+ T cells (Tn/Tm) were measured by flow cytometry. The percentage of CD4+ naïve T (Tn), CD8+ Tn, CD8+ T memory stem cell (Tscm), and CD8+ terminal effector T cell decreased obviously. Still, all AC of Tn/Tm of aNSCLCs was significantly lower compared to NCs. Higher AC and percentage of CD4+ Tn, CD8+ Tn, and CD4+ Tscm showed markedly longer median PFS in aNSCLCs. Statistics demonstrated the AC of CD4+ Tn (≥ 3.7 cells/μL) was an independent protective factor for PFS. The analysis of the prognosis of immunotherapy showed the higher AC and percentage of CD4+ Tn and CD4+ Tscm and higher AC of CD8+ Tscm had significantly longer median PFS and the AC of CD4+ Tn (≥ 5.5 cells/μL) was an independent protective factor for PFS. Moreover, higher AC and percentages of Tn/Tm suggested higher disease control rate and lower progressive disease rate. The AC of Tn/Tm showed more regular patterns of impairment and was more relative with the disease progression than percentages in aNSCLCs. AC had a better predictive value than percentages in Tn/Tm for PFS. Notably, the AC of CD4+ Tn was a potential prognostic biomarker for the PFS and efficacy of immunotherapy.

Cryptococcal Antigen Screening and Missed Opportunities for Earlier Diagnosis Among People With HIV and Poor Virologic Control in the Bronx, NY.

Background:There is no established cryptococcal antigen (CrAg) screening guideline for people with HIV who are antiretroviral therapy experienced but have poor virologic control. We assessed factors associated with CrAg screening and describe missed opportunities for earlier testing.Setting:Ambulatory clinics affiliated with Montefiore Medical Center, Bronx, NY.Methods:This was a retrospective chart review of CrAg screening among asymptomatic people with HIV with absolute CD4 counts200 cells/mm3 and HIV viral loads (VLs) > 200 copies/mL receiving HIV care from 2015 to 2020. We used Cox proportional hazards regression to identify predictors of screening, including longitudinal CD4 count and HIV VL as time-varying covariables. Among cases of diagnosed cryptococcosis, we assessed for opportunities for earlier diagnosis.Results:Screening CrAg was performed in 2.9% of 2201 individuals meeting the inclusion criteria. Compared with those not screened, those who were screened had a shorter duration of HIV infection (0.09 vs. 5.1 years; P = 0.001) and lower absolute CD4 counts (12 vs. 24 cells/mm3; P < 0.0001). In a multivariable model stratified by median HIV duration, CD4 < 100 [hazard ratio (HR), 7.07; 95% confidence interval (CI): 2.43 to 20.6], VL > 10,000 (HR, 15.0; 95% CI: 4.16 to 54.0), and a shorter duration of HIV infection (HR, 0.60; 95% CI: 0.42 to 0.86) were associated with screening for those with HIV < 5 years. Among those diagnosed with cryptococcosis (n = 14), 6 individuals had an ambulatory visit in the preceding 6 months but did not undergo screening.Conclusion:CrAg screening was infrequently performed in this at-risk population. Those with a longer duration of HIV infection were less likely to undergo CrAg screening, highlighting potential missed opportunities for earlier diagnosis.

Functional state of regulatory CD4+T cell pool in HIV/hepatitis C virus coinfected subjects

Coinfection with HIV and hepatitis C virus (HCV) leads to development of systemic inflammation associated with increased risk for liver, kidney and cardiovascular diseases, as well as higher mortality from AIDS-associated and non-AIDS-associated illnesses. To a large extent, systemic inflammation is controlled by regulatory T lymphocytes, a subset of CD4+ T cells. While expressing various functional molecules, regulatory CD4+T cells limit functional activity of immunocytes and prevent the development of excessive inflammatory reactions and autoimmune diseases. At the same time, there are no available data in literature concerning the sizes of certain functionally active regulatory CD4+T cell subsets in HIV/HCV coinfected patients. Our aim was to estimate the size of functional pool of the regulatory CD4+T lymphocytes in HIV/ HCV coinfected patients receiving antiretroviral therapy.&#x0D; Two groups of HIV-positive patients were examined: 1) HIV/HCV coinfected subjects (n = 21); 2) HIV mono-infected patients (n = 22). The control group included voluntary blood donors without HIV and HCV infections (n = 23). Regulatory CD4+T lymphocytes were identified by multicolor flow cytometry based on the expression of the following markers: CD3, CD4, CD25, CD127, and FoxP3. Functional subsets of regulatory CD4+T cells were discerned by the expression of CD39, GARP, LAP, and CD71 molecules. Relative and absolute counts of suppressor CD4+T lymphocytes were calculated for each subset. TGF-1 concentrations in blood plasma were determined with ELISA technique.&#x0D; Absolute counts of regulatory CD4+T lymphocytes in peripheral blood of HIV/HCV coinfected patients proved to be twice lower than in healthy subjects, while being not accompanied by a decrease in relative frequency of these cells. Despite their deficiency, the number of functionally active CD39-positive,&#x0D; GARP/LAP-positive, and CD71-positive suppressor cells in HIV/HCV coinfected persons remained at the level found in HIV-monoinfected and healthy people. The frequency of functionally active regulatory CD4+T lymphocytes was increased in HIV/HCV coinfected patients compared with HIV-monoinfected (CD39+, GARP+LAP+) and healthy (CD39+, GARP+LAP+, CD71+) subjects.&#x0D; In HIV/HCV coinfected patients receiving antiretroviral therapy, the pool of regulatory CD4+T lymphocytes is rich in cells possessing high suppressive capacity. However, the absolute number of functionally active regulatory CD4+T cells remain at the level corresponding to healthy individuals, thus, apparently, is not sufficient to control the systemic inflammation developing in HIV/HCV coinfection.

Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition.

In some instances, unsuppressed HIV has been associated with severe COVID-19 disease, but the mechanisms underpinning this susceptibility are still unclear. Here, we assessed the impact of HIV infection on the quality and epitope specificity of SARS-CoV-2 T cell responses in the first wave and second wave of the COVID-19 epidemic in South Africa. Flow cytometry was used to measure T cell responses following peripheral blood mononuclear cell stimulation with SARS-CoV-2 peptide pools. Culture expansion was used to determine T cell immunodominance hierarchies and to assess potential SARS-CoV-2 escape from T cell recognition. HIV-seronegative individuals had significantly greater CD4+ T cell responses against the Spike protein compared to the viremic people living with HIV (PLWH). Absolute CD4 count correlated positively with SARS-CoV-2-specific CD4+ and CD8+ T cell responses (CD4 r=0.5, p=0.03; CD8 r=0.5, p=0.001), whereas T cell activation was negatively correlated with CD4+ T cell responses (CD4 r=-0.7, p=0.04). There was diminished T cell cross-recognition between the two waves, which was more pronounced in individuals with unsuppressed HIV infection. Importantly, we identify four mutations in the Beta variant that resulted in abrogation of T cell recognition. Taken together, we show that unsuppressed HIV infection markedly impairs T cell responses to SARS-Cov-2 infection and diminishes T cell cross-recognition. These findings may partly explain the increased susceptibility of PLWH to severe COVID-19 and also highlights their vulnerability to emerging SARS-CoV-2 variants of concern.

Immune Cells Profiles In The Peripheral Blood Of Patients With Moderate To Severe COVID-19 And Healthy Subjects With and Without Vaccination With The Pfizer-BioNTech mRNA Vaccine.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), has caused a global crisis. Patients with COVID-19 present with a range of clinical manifestations, from no symptoms to severe illness. However, little is known about the profiles of immune cells required to protect against SARS-CoV-2. This study was performed to determine the immune cells profiles in the peripheral blood of COVID-19 patients with moderate to severe disease (n=52), and compare the findings with those from healthy subjects vaccinated with Pfizer BioNTech mRNA vaccine (VS) (n=62), and non-vaccinated healthy subjects (HS) (n=30) from Kuwait. Absolute counts and percentages of total lymphocytes and lymphocyte subsets (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+CD56+ NK cells) in the peripheral blood of the three groups were analyzed using flow cytometry. The results showed that the absolute counts of total lymphocytes, CD3+, CD4+, and CD8+ T cells, CD19+ B cells, and CD56+ NK cells, were significantly lower in COVID-19 patients than normal healthy controls and vaccinated subjects. The percentages of CD3+ and CD4+ T lymphocytes were also significantly lower in the COVID-19 patients. However, the percentage of CD16+CD56+ NK cells was significantly higher in the peripheral blood of COVID-19 patients, compared to the HS and VS groups with no detectable differences in the percentages of CD8+ T cells and CD19+ B cells between the three groups. Analysis of the monocyte subsets has showed a significantly higher percentage of CD14+HLA-DR+ monocytes in COVID-19 patients compared to HS whereas the inflammatory CD14+CD16+ HLA-DR+ monocytes, and the non-classical CD16+HLA-DR+ monocytes showed significantly lower frequency in the blood of the patients than that of HS. These findings demonstrate perturbations of both innate and adaptive immune cell subsets that reflect dysregulated host responses in COVID-19 patients with moderate to severe disease.

Effect of Somatosensory Interaction Transcutaneous Electrical Acupoint Stimulation on Cancer-related Fatigue and Immunity: A Randomized Controlled Trial.

Background:This study was intended to evaluate the clinical effect of somatosensory interaction transcutaneous electrical acupoint stimulation (SI-TEAS) on cancer-related fatigue (CRF) and its safety.Methods:The study protocol had been registered in China Clinical Trial Registration Center with registration number: ChiCTR2100045655. CRF patients were equally divided into SI-TEAS Group, Acupressure Group and Sham Acupressure Group to receive SI-TEAS, acupressure and sham acupressure treatments 5 times a week. The fatigue levels of patients in the 3 groups were measured by the Piper Fatigue Scale during the baseline period and after 4 and 8 weeks (of treatment). The cell immunity of these patients was determined by detecting the T-lymphocyte subsets and NK cells.Result:Of the 300 participants, 279 have gone through the independent rehabilitation intervention study, including 94 in the SI-TEAS Group, 92 in the Acupressure Group, and 93 in the Sham Acupressure Group. Intergroup comparisons of fatigue degree and cell immunity, namely SI-TEAS Group versus Acupressure Group, Acupressure Group versus Sham Acupressure Group, and SI-TEAS Group versus Sham Acupressure Group, showed that group changes observed during the baseline period and different time points after Week 4 and 8 were statistically different (P<0.05). The SI-TEAS Group had the sharpest decreases in the behavioral, sensory, emotional and cognitive dimensions of fatigue, and the total score, followed by the Acupressure Group, while the Sham Acupressure Group did not show significant changes; the SI-TEAS Group experienced the sharpest increases in the absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD4+/CD8+ T cells, and NK cells, followed by the Acupressure Group, while the Sham Acupressure Group did not show significant changes.Conclusion:SI-TEAS could significantly relieve the fatigue of CRF patients and improve their cell immunity, which maybe a useful and effective option for reducing CRF in clinical practice.

MO429: The Association of Circulating Monocytes Subsets, NK Cells and Lymphocyte Subpopulations With Conventional and Novel Deformation Indices of Left Ventricular Function in CKD Patients With No Established Cardiovascular Disease

Abstract BACKGROUND AND AIMS Cardiovascular disease (CVD) and chronic kidney disease (CKD) are closely interrelated. Adverse immune responses have been implicated in the pathogenesis of both CVD and CKD [1, 2]. Monocyte subsets are key in atherogenesis and the inflammatory cascade occurring in heart failure [1, 2]. Likewise, the role of lymphocyte subpopulations including natural killer (NK) cells and CD4 + CD25 + regulatory T cells (Tregs) in the modulation of inflammation and immunity and subsequent cardiovascular implications have received increasing attention [2]. The implication of immune cells subsets in the abnormal myocardial remodeling as universally occurs in CKD patients even without overt CVD, remains to be clarified [3]. The aim of our study was to investigate potential correlations between blood levels of specific immune cells subsets with conventional and novel deformation-related indices of LV function in a cohort of patients with CKD without established CVD. METHOD A total of 35 stable CKD patients (mean age 66 ±12.2 years, 57% males, 20% diabetics) without established CVD were included in the study. Exclusion criteria included the history of malignancy, autoimmune disease and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16 + and CD14 + CD16++ percentage and absolute number of cells out of the total monocytes and NK cells (CD3 + CD16 + 56+), CD3-CD19 + B lymphocytes, CD3 + CD4 + T cells, CD3 + CD8 + T cells and Tregs (CD4 + CD25 + FoxP3+) absolute values and percentage out of the total lymphocytes were measured by flow cytometry. Simultaneously, conventional [left atrial volume index (LAVI), LV mass index (LVMI), LV end-diastolic volume (LVEDV), E/E’] and novel 2D speckle tracking (2DST) echocardiographic indices of LV function [global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), TWIST and UNTWIST] were assessed. RESULTS The mean estimated glomerular filtration rate (eGFR) was 28 ±15 mL/min/1.73 m2 (CKD-EPI) and the mean 24-h proteinuria was 2457 ±2399 mg. The percentage of total blood lymphocytes, as well as both percentage and absolute counts of CD4 + T-cells, were positively correlated with the eGFR (P &amp;lt; 0.05 and &amp;lt; 0.01 respectively) whereas. In addition, both NK cells percentage (P &amp;lt; 0.05) and absolute values (P &amp;lt; 0.01) showed a negative association with proteinuria. Regarding classical indices of LV function, NK counts were negatively associated with LVEDV (P &amp;lt; 0.05). An increased percentage of intermediate CD14++CD16 + monocytes was positively associated with the GRS (P &amp;lt; 0.005). Furthermore, the percentage of T-cells and CD8 + T-cells were positively associated with LV TWIST whereas a positive association was found between the percentage of CD8 + T-cells and more negative values of LV UNTWIST (P &amp;lt; 0.05). No specific significant correlations were observed between the rest immune cells subpopulations with either the classical or the novel indices of LV dysfunction. CONCLUSION The results of our study suggest that alterations of immune cells subsets correlate with subclinical markers of LV dysfunction in CKD patients without established CVD. The significance of the implication of the cellular arm of the immune system in the pathophysiological pathways of specific CVD phenotypes in CKD and the utility of immune cells subsets as tools to identify CKD patients who are at the highest risk for developing complications shall be elucidated by future research.

Reduced Counts of Various Subsets of Peripheral Blood T Lymphocytes in Patients with Severe Course of COVID-19.

This study was intended to define T lymphocyte subsets in different clinical groups of COVID-19-infected patients to explore the interaction between T cell-mediated immune response and the severity of COVID-19 course. Lymphopenia in patients with severe COVID-19 was found. In patients with severe COVID-19 course, the absolute counts of CD3+, CD4+, and CD8+ T lymphocytes at admission were lower than on day 14 after discharge. Further analysis showed that the older were the patients with COVID-19, the more likely they developed severe infection. The results confirmed the significance of T lymphocytes in the clearance of the COVID-19.

Hiv Stage 4 With Pulmonary Tuberculosis, Collitis Tuberculosis, Oral Candidiasis, Wasting Syndrome, And Sensorineural Deafness: A Case Report

Human immunodeficiency virus (HIV) is a retrovirus type virus that infects cells of the human immune system (especially CD4 positive T-cells and major components of the cellular immune system) and interferes with their function. This viral infection results in a continuous decline in the immune system, which will result in immune deficiency. People who are immune deficient/immunodeficiency become more susceptible to various types of infections. A 23 year male, a cafe employee, was admitted to hospital with complaints of weakness since 2 weeks before. He has productive cough for 3 weeks. He had decrease of food appetite, nauseas and vomiting. He had weight loss about 10 kg in the last 4 months. Patient had history of free sex, LGBT, since 2016 and history of hearing loss for 3 months. Laboratory finding showed rhonchi were found at the apex of the right and left lungs, Anti-HIV reactive and Absolute CD-4 count was 53 cell/uL, Gene Xpert MTB was detected, and Acid fast bacilli in stool is positive. Audiometry showed bilateral sensorineural deafness. Patient was diagnosed with HIV stage 4 with pulmonary tuberculosis, tuberculosis collitis, oral candidiasis, wasting syndrome, and sensorineural deafness.

In Patients with Severe COVID-19, the Profound Decrease in the Peripheral Blood T-Cell Subsets Is Correlated with an Increase of QuantiFERON-TB Gold Plus Indeterminate Rates and Reflecting a Reduced Interferon-Gamma Production.

Increased rates of indeterminate QuantiFERON-TB Gold Plus Assay (QFT-Plus) were demonstrated in patients hospitalized with Coronavirus Disease (COVID)-19. We aimed to define the prevalence and characteristics of hospitalized COVID-19 patients with indeterminate QFT-Plus. A retrospective study was performed including hospitalized COVID-19 patients, stratified in survivors and non-survivors, non-severe and severe according to the maximal oxygen supply required. Statistical analysis was performed using JASP ver0.14.1 and GraphPad Prism ver8.2.1. A total of 420 patients were included, median age: 65 years, males: 66.4%. The QFT-Plus was indeterminate in 22.1% of patients. Increased rate of indeterminate QFT-Plus was found in non-survivors (p = 0.013) and in severe COVID-19 patients (p < 0.001). Considering the Mitogen-Nil condition of the QFT-Plus, an impaired production of interferon-gamma (IFN-γ) was found in non-survivors (p < 0.001) and in severe COVID-19 patients (p < 0.001). A positive correlation between IFN-γ levels in the Mitogen-Nil condition and the absolute counts of CD3+ (p < 0.001), CD4+ (p < 0.001), and CD8+ (p < 0.001) T-lymphocytes was found. At the multivariable analysis, CD3+ T-cell absolute counts and CD4/CD8 ratio were confirmed as independent predictors of indeterminate results at the QFT-Plus. Our study confirmed the increased rate of indeterminate QFT-Plus in COVID-19 patients, mainly depending on the peripheral blood T-lymphocyte depletion found in the most severe cases.

Characteristics of the Gut Microbiome and Its Relationship With Peripheral CD4+ T Cell Subpopulations and Cytokines in Rheumatoid Arthritis.

This study investigated the association between intestinal microbiota abundance and diversity and cluster of differentiation (CD)4+ T cell subpopulations, cytokine levels, and disease activity in rheumatoid arthritis RA. A total of 108 rheumatoid arthritis (RA) patients and 99 healthy control (HC) subjects were recruited. PICRUSt2 was used for functional metagenomic predictions. Absolute counts of peripheral CD4+ T cell subpopulations and cytokine levels were detected by flow cytometry and with a cytokine bead array, respectively. Correlations were analyzed with the Spearman rank correlation test. The results showed that the diversity of intestinal microbiota was decreased in RA patients compared to HCs. At the phylum level, the abundance of Firmicutes, Fusobacteriota, and Bacteroidota was decreased while that of Actinobacteria and Proteobacteria was increased and at the genus level, the abundance of Faecalibacterium, Blautia, and Escherichia-Shigella was increased while that of Bacteroides and Coprococcus was decreased in RA patients compared to HC subjects. The linear discriminant analysis effect size indicated that Bifidobacterium was the most significant genus in RA. The most highly enriched Kyoto Encyclopedia of Genes and Genomes pathway in RA patients was amino acid metabolism. The relative abundance of Megamonas, Monoglobus, and Prevotella was positively correlated with CD4+ T cell counts and cytokine levels; and the relative numbers of regulatory T cells (Tregs) and T helper (Th17)/Treg ratio were negatively correlated with disease activity in RA. These results suggest that dysbiosis of certain bacterial lineages and alterations in gut microbiota metabolism lead to changes in the host immune profile that contribute to RA pathogenesis.

Performance Evaluation of BD FACSPrestoTM Near-Patient CD4 Counter for Monitoring Antiretroviral Therapy in HIV-Infected Individuals in Primary Healthcare Clinics in Thailand.

HIV viral load is more reliable tool for monitoring treatment throughout the course of HIV/AIDS, but the test may be expensive in resource-limited settings. Therefore, enumeration of CD4 T-lymphocyte count remains important in these settings. This study evaluated the performance of BDFACSPresto, a near-patient CD4 counter planned to be used in primary healthcare clinics in Thailand. Results of percent, absolute CD4 count and hemoglobin (Hb) on the FACSPresto were compared with the TriTEST/TruCOUNT/BDFACSCalibur method and a Sysmex hematology analyzer. Phase I of the study was performed in an ISO15189 laboratory. Both percentage and absolute values showed Passing–Bablok slopes within 0.98–1.06 and 0.97–1.13, mean Bland–Altman biases of +1.2% and +20.5 cells/µL, respectively. In phase II, venous and some capillary blood samples were analyzed in four primary healthcare clinics. The results showed good correlation between capillary and venous blood. For venous blood samples, regression lines showed slopes of 1.01–1.05 and 1.01–1.07 for all percentage and absolute values. The overall mean biases were +0.9% and +17.0 cells/µL. For Hb, Passing–Bablok regression result gave slope within 1.01–1.07 and mean bias of −0.06 g/dL. Thus, CD4 enumeration in blood by the FACSPresto is reliable and can be performed to an identical standard at primary healthcare clinics.

Disseminated histoplasmosis mimicking hematologic malignancy in a patient with human immunodeficiency virus.

A 25-year-old recent immigrant from El Salvador with a known human immunodeficiency virus (HIV) infection was transferred to the University of Maryland Greenebaum Comprehensive Cancer Center with altered mental status, fever, epistaxis, gingival hemorrhage, melena, and rash. He was cachectic and acutely ill, with axillary and inguinal adenopathy and a palpable spleen tip. Hemoglobin was 66 g/L, white blood cell (WBC) count 6.6 × 109/L with 38% segmented neutrophils, 10% bands, 11% metamyelocytes, 13% myelocytes, 6% blasts and 200 nucleated red blood cells per 100 WBC, and platelet count 64 × 109/L. Creatinine was 472 μmol/L, lactate dehydrogenase 15,983 iu/L, and uric acid 702 μmol/L. HIV viral load was 82,040 copies/ml and absolute CD4 count was 16 cells/dl. Computerized tomography of the chest and abdomen showed extensive upper mediastinal and axillary adenopathy, bilateral pleural effusions, scattered retroperitoneal, mesenteric and inguinal adenopathy, splenomegaly, and ascites. The presumed diagnosis was a hematologic malignancy. However, the peripheral blood smear demonstrated not only leukoerythroblastic changes, including nucleated red blood cells (A) and myelocytes (B) but also intracytoplasmic yeast organisms in myelocytes (B) and neutrophils (C), and bone marrow aspirate (D) and biopsy (E, F) showed prominent histiocytosis with innumerable intracellular ovoid yeast forms. The patient was diagnosed with disseminated histoplasmosis involving blood, bone marrow, skin and cerebrospinal fluid, as well as mycobacterium avium complex and klebsiella septicemia, complicating uncontrolled HIV infection. He responded to antibiotics, including a 6-week course of liposomal amphotericin B. Uncontrolled HIV infection is rare in the setting of currently available highly active antiretroviral therapy, but does occur, and can be complicated by disseminated opportunistic infections, as well as by high-grade lymphomas and other malignancies. Leukoerythroblastosis, defined by the presence of nucleated red blood cells and immature myeloid cells in the circulating blood, can be caused by malignant bone marrow infiltration, but also by disseminated infection. Our patient's bone marrow failure, leukoerythroblastosis, and extensive lymphadenopathy were caused by disseminated histoplasmosis, rather than by a hematologic malignancy. NIH-NCI, Grant/award no: P30 CA134274. The authors declare that they have no conflict of interest.

Classification of Absolute Cd4+ T Lymphocytes Count in Immunological, Virological and Erythropoietic Growth Factor among HIV Infected Patients

Background: HIV-infection resulted in CD4+ T-cell depletion which is accompanied by an increase in CD8+ T-cells resulting in an inverted CD4/CD8 ratio. Low CD4/CD8 ratio has been identified as a hallmark of inmmunosenescence and a surrogate of mortality in HIV infected patients especially in ART-naïve patients Aim: Classification of absolute CD4+ T-lymphocytes count in immunological, virological and erythropoietic growth factor among HIV infected patients Methodology: One hundred samples each was collected from HIV positive subjects on ART and HIV positive subjects ART naïve. Six milliliters of whole blood was collected from each consented subject, 3ml was dispensed into 5ml K2EDTA bottle for immediate analysis of absolute CD4 count, CD8 count, total white cell count and HIV screening. The remaining 3ml of blood was dispensed into plain bottle; serum was extracted for the analysis of erythropoietin and viral load Results: Mean values of CD8, CD4/CD8, EPO and TWBC in CD4 &lt;200 were significantly (p&lt;0.05) lower compared to CD4 &gt;500 and CD4 200-499. Mean values of VL in CD4 &lt;200 were significantly (p&lt;0.05) higher compared to CD4 &gt;500 and CD4 200-499 among HIV subjects on ART and ART-naïve Conclusion: Immunological and erythropoetic growth factor assessed in this study were decline while viral load was increasing as HIV infection progresses with depletion in absolute CD4 count, this study shows the efficacy of ART on the treated subjects. However, based on this study, absolute CD8 T cells count, CD4/CD8 ratio and erythropoietin can be used as surrogate makers to ascertain pathogenesis in HIV-infected subjects.

Lymphocyte Phenotyping and HLA-DR Expression over the Course of COVID-19 Infection in Patients with Different Disease Severity.

The role of lymphocyte subsets in the diagnosis and follow up of COVID-19 is still unclear. So, we aim to study the changes in lymphocyte subsets and HLA-DR expression in the peripheral blood of hospitalized COVID-19 patients. Lymphocyte subsets and HLA-DR expression were detected in the peripheral blood of 36 hospitalized patients of COVID-19; their data were compared to that of 36 healthy controls of comparable age and gender. Total lymphocytes, the percentage of CD3 T, CD4 T and CD8 T cells significantly decreased, while that of CD 56 cells significantly increased in SARS-CoV-2 infected patients. The expression of HLA-DR is down regulated in these cells. Neutrophil/lymphocyte ratio, neutrophil/CD3 ratio, neutrophil/CD4 ratio, and neutrophil/CD8 ratio are significantly increased in patients compared with controls. The absolute count of CD3, CD4, CD8 and CD19 cells, significantly decreased in SARS-CoV-2 infected patients. A marked reduction in CD8+T and CD4+T count together with HLA-DR cell expression with obvious impairment in cellular immunity has been detected in patients with more severe impairment and progressive course for the disease.

Incidence and predictors of nevirapine and efavirenz-associated rash among Indonesian HIV patients

Many drugs used for the treatment of HIV disease can cause drug hypersensitivity reactions. Since 2002, World Health Organization (WHO) has recommended the use of nevirapine and efavirenz as part of first line antiretroviral therapies for several years. Both of the drugs had equivalent clinical efficacy but differences in toxicity profile. We aimed to determine the incidence and predictors of nevirapine and efavirenz-associated rash among Indonesian HIV-infected patients. A retrospective cohort study was conducted among Indonesian patients who were using nevirapine or efavirenz between January 2004 to December 2013. All eligible predictors were analyzed using bivariate and multivariate analysis. 2,071 patients received nevirapine and 1,212 received efavirenz as first line therapies. The cumulative incidence of nevirapine-associated rash was 14% (95%CI: 12.5-15.5%) and evafirenz-associated rash was 4.5% (95%CI: 3.4-5.8%). Severe reactions occurred 1% patients receiving NVP and 0.1% patients receiving EFV, but no patients died due to these conditions. Predictors independently related with nevirapine-associated rash were female gender (adjusted RR = 1.622; 95%CI: 1.196-2.199; p = 0.002), baseline absolute CD4 count above 200 cells/mm3 (adjusted RR = 1.387; 95%CI: 1.041-1.847; p = 0.025), and hepatitis C co-infection (adjusted RR = 1.507; 95%CI: 1.138-1.995; p = 0.004). Baseline ALT level > 1.25 times upper normal limit (adjusted RR = 1.508; 95%CI: 0.998-2.278; p = 0.051) had a tendency to be a good predictor. None of the risk factors investigated was associated with developing efavirenz-associated rash. Female, baseline absolute CD4 count above 200 cells/mm3, hepatitis C co-infection and baseline ALT levels more than 1.25 times upper normal limit were predictors for nevirapine-associated rash in HIV patients.