CD4 Count Research Articles

Diagnoses of children living with HIV before and during the COVID-19 pandemic.

There is limited data on diagnoses during hospital stay among children living with HIV(CLHIV) in the antiretroviral and coronavirus disease 2019 (COVID-19) era. The aim of this study was to describe hospital diagnoses and clinical characteristics of CLHIV before and during the COVID-19 pandemic. A retrospective descriptive cross-sectional study was performed. Clinical and laboratory data were retrieved by reviewing folders and discharge summaries from January 2019 to December 2021. Period A (pre-COVID-19) was defined as the period from January 2019 to March 2020. Period B (During COVID-19) was defined as being from April 2020 to December 2021. Ninety-six children contributed 215 diagnoses over the study period. The five most common diagnoses were unspecified HIV disease (47/215, 21.9%), tuberculosis (TB) (42/215, 19.5%), pneumonia (13/215, 6.0%), encephalopathy (11/215, 5.1%) and malnutrition (11/215, 5.1%). Median CD4 count was 377 cells/mm (IQR 126, 726) and 8.0% of the children were virally suppressed. Ninety-five per cent of the children had WHO Stage 3 and 4 (95%) disease and 12.5% of children required ICU admission. No child was diagnosed with COVID-19 despite universal screening. Moreover, 81.7% of the children had a social worker referral documented. Advanced HIV disease (AHD) remains prevalent with TB being the most common diagnosis. There were no cases of COVID-19 recorded in CLHIV. The findings provide a description of the diagnoses of CLHIV in the South African setting prior to and during the COVID-19 pandemic. It highlights the need for more specific documentation of diagnoses to inform better prevention of AHD in children.

Effect of interleukin 1b inhibition with canakinumab on inflammation and viral persistence in people with human immunodeficiency virus

Abstract Introduction Effectively treated people with HIV (PWH) have elevated risk of cardiovascular disease (CVD). Inflammatory markers are predictive of CVD and mortality among PWH. The role of the myeloid system in driving inflammation and atherosclerosis has been recently recognized. Canakinumab (a monoclonal antibody to IL-1β) reduces inflammation and CVD events among people with elevated hsCRP after myocardial infarction without HIV. We evaluated the impact of IL-1β inhibition using canakinumab on HIV parameters, inflammation, HIV persistence markers, arterial inflammation, and hematopoietic activity in PWH. Methods PWH on effective ART who had CVD or were at risk for CVD were randomized 2:1 to receive 150 mg of canakinumab subcutaneously or matched placebo at weeks 0 and 12. Arterial inflammation and bone marrow metabolic activity were assessed using F18 FDG PET/CT at baseline and week 18. T cell and monocyte activation were evaluated using multiparameter spectral cytometry. The viral reservoir was quantified using Tat/rev Induced Limiting Dilution Assay (TILDA), HIV DNA and cell-associated RNA. The primary endpoints were change in CD4 and CD8 count. We assessed group effects over time using linear mixed effects models. Results 33 individuals were randomized (median age of 60 years old (IQR 57.5, 64.5) and 94% male); 25 received canakinumab and 8 received placebo. There were no significant differences at baseline. As expected, IL-1β increased among those treated with canakinumab at weeks 4- 24 (p<0.01 for each) and returned to baseline at week 36. There was one death from sepsis in an individual aged 84 with CVD and poorly controlled diabetes who received canakinumab. There were no significant changes in CD4 count, CD8 count, platelet count, creatinine, AST, or ALT by group. Treatment was not associated with a greater reduction in arterial inflammation in the most diseased segment compared to placebo (-6.9%; 95% CI -30.4 to 24.5%; p=0.62). However, bone marrow metabolic activity decreased in the canakinumab group versus placebo (-14.4%, 95% CI -26.5% to -0.2%; p=0.047). Treatment was associated with increased CD163 expression on monocytes at weeks 24 (p=0.03) and 36 (p<0.001), and lower caspase activity at week 36 (p=0.02). There was expansion of anti-inflammatory CD16+ patrolling monocytes that co-express CD163+CX3CR1+ and a decrease in pro-inflammatory CD16+ patrolling monocytes that are Caspase1+CCR2+. Treatment was not associated with differences in hsCRP, IL-6, IL-16, IL-18, MCP-1, sCD14, sCD163, T cell subsets, NK cell subsets, or viral persistence markers. Conclusion Among treated PWH, targeted inhibition of IL-1β using canakinumab results in decreased bone marrow metabolic activity and a shift toward anti-inflammatory monocyte populations. These findings shed light on mechanisms underlying how targeted IL-1β inhibition using canakinumab prevents CVD events by altering monocyte populations and reducing systemic inflammation.

Exploring the associations of tobacco smoking and serum cotinine levels with selected inflammatory markers in adults with HIV in South Africa

This study examined the associations between tobacco smoking and serum cotinine levels, an objective biochemical measure of tobacco smoke exposure, with markers of inflammation, i.e., interferon-gamma (IFN-γ), interleukin 10 (IL-10), interleukin 2 (IL-2) and tumour necrosis factor-alpha (TNF-α) in people living with HIV (PLWH).These specific markers were selected because of their hypothesised associations with smoking, PLWH and their outcomes. In a random sample of ≥ 18-year-old PLWH receiving care at 17 public healthcare facilities across the Western Cape Province in South Africa, data collection included self-reported smoking history, and serum levels of cotinine and selected inflammatory markers. The inflammatory marker data were log transformed because of the skewedness of their distribution. Linear regression models (1) adjusted for age and gender, and (2) fully adjusted for age, gender, current alcohol use, body mass index and CD4 counts were used to examine the associations between smoking tobacco or serum cotinine and inflammatory markers. Level of significance was p < 0.05. Among 749 PLWH who were mainly women (79%), the mean age was 38.5 (8.9) years and similar when stratified by smoking status. Serum cotinine levels exhibited a striking discrepancy, with a median of 154 ng/mL among current smokers, in stark contrast to the consistent median values of 10 ng/mL observed among past and never smokers. In regression models adjusted for age and gender, current smoking and frequent smoking were associated with lower IL-2 but higher TNF-α. Log-cotinine exhibited associations with IFN-γ, IL-10, and TNF-α, while cotinine levels ≥ 10 ng/mL compared to < 10 ng/mL were associated with higher IFN-γ and TNF-α. In fully adjusted models, log-cotinine and cotinine levels ≥ 10 ng/mL displayed significant associations with higher IFN-γ and lower IL-2. This study underscores the importance of investigating the interplay between smoking tobacco or serum cotinine levels with pro-inflammatory cytokines in PLWH. It signals the need for comprehensive research to unravel the potential synergistic impacts of smoking tobacco and HIV infection on chronic inflammation and immune dysregulation, shedding light on critical avenues for intervention and management strategies.

Subclinical myocardial disfunction detected by left ventricle myocardial work impairment in patients with long standing human inmmunodeficiency virus infection

Abstract Heart failure is a known complication in patients living with human inmmunodeficiency virus (HVI) infection. Detection of subclinical disfunction is nowadays possible by echocardiographic strain techniques. Myocardial work is a novel technique based on global longitudinal strain (GLS) that measures global work efficiency of left ventricle (GWE) and would allow early detection of subclinical myocardial damage. Methods We performed a cross sectional echocardiographic study of patients with long standing HIV infection, and no previous cardiopathy, assessing GLS of left ventricle (LV), left atrium (LA) and free wall of right ventricle (RV-FW GLS). We identified patients with subclinical disfunction expressed by an impaired GWE , and studied its determinants by lineal regression. Results 110 patients, 78.2% male, median age 53.3 (51.2-55.4) were included. Time from diagnosis was 20.5 (18.6-22.3) years. Myocardial work strain analysis showed an impaired GWE: 91.9% (90.9-92.9);p&amp;lt;0.001) and a GW index of 1840.8 mmHg%(1758.7-1922.9):p&amp;lt;0.001. The rest of deformation parameters laid into normal range: LV GLS was -19.5% (-19.0- -20.0) GLS dispersion 55.1 (50.1-60.1), LA GLS (reservoir) 32.8% (31.2-34.5), and RV free wall GLS -22.3% (-21.4 - -23.2). By univariate analysis, determinants of impaired GWE were age, Score2 risk, time from HIV diagnosis, QRS Interval duration, long QTc Interval, LV ejection fraction (LVEF),diastolic disfunction by doppler tissue imaging, CD4 count nadir, initial and maximun viral load, and exposure to didanosine treatment. After adjustment by cardiovascular risk and diastolic function (Ea velocity by tissue Doppler) , GWE impaired depended on duration of infection (Beta 0.3;95%CI:0.04-0.56;p=0.023), initial viral load (Beta -1.1;95%CI:-2.1- -0.02;p=0.046) and exposure to stavudine (Beta -6.3;95%IC: -11.5- -1.1;p=0.019). Conclusions Subclinical myocardial disfunction is prevalent in long standing HIV infection. Global work efficiency is a very sensitive parameter for detection, even in patients with normal GLS values, and it was related to duration of infection, initial viral load, and exposure to stavudine in our patients.Determinants of Global Work Efficiency

Thrombus aspiration in people living with HIV- a night mare for interventionist

Abstract Background Cardiovascular disease, particularly atherosclerosis, and its complications are a growing cause of morbidity and mortality among individuals living with human immunodeficiency virus (HIV) in the post-antiretroviral therapy era. The role of thrombus aspiration combined with primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) within this population remains contentious. While PCI is the preferred strategy for immediate revascularization in acute STEMI, challenges persist, with about 30% of patients experiencing persistent chest pain and ST-segment elevation despite achieving TIMI III flow in the culprit vessel. Methods We conducted a prospective observational study spanning from January 2015 to September 2023, involving ten consecutive HIV-infected patients presenting with STEMI to our acute coronary care unit. The study encompassed an analysis of baseline clinical characteristics, response to fibrinolytic therapy, angiographic findings, thrombus aspiration using the Export Aspiration Catheter, and the outcomes of percutaneous coronary intervention (PCI). Patients were closely monitored for in-hospital outcomes and followed up for five years, during which they received adjuvant highly active antiretroviral therapy (HAART). Results The mean age of the patients was 46 years, lower than their uninfected counterparts. Most patients presented with a lower Killip class, indicating favorable outcomes. CD4 count distribution showed variability, with ten patients undergoing rescue angioplasty with thrombus aspiration using the Export Catheter. The cohort was followed for five years, receiving consistent HAART therapy. Conclusion HIV-associated atherosclerosis presents a considerable health burden, characterized by distinctive non-calcified and inflammatory plaques vulnerable to rupture. Thrombus aspiration during PCI emerged as a valuable strategy, reducing thrombotic burden and contributing to improved clinical outcomes in people living with HIV.

COMPREENDENDO A INTERSEÇÃO ENTRE HIV/AIDS E PNEUMONIA: UMA ANÁLISE ABRANGENTE DA LITERATURA

INTRODUCTION: The relationship between HIV/AIDS and pneumonia is complex and multifaceted. Individuals infected with HIV have a significantly higher risk of developing pneumonia, caused by both bacterial and viral agents, due to immune suppression from the virus. OBJECTIVE: To identify in the literature the relationship between HIV/AIDS and pneumonia in the context of nursing care. MATERIALS AND METHODS: This is an integrative literature review conducted in the MEDLINE, LILACS, and BDENF databases, using the descriptors: “HIV seropositivity,” “Pneumonia,” and “nursing care.” The descriptors were combined using the boolean operator AND, covering the period from 2018 to 2024. RESULTS: The study found that HIV-positive patients tend to experience a subacute progression of Pneumocystis jirovecii pneumonia (PCP), while immunocompromised patients without HIV face rapid progression, with a higher risk of respiratory failure and mortality. CT scans showed ground-glass opacities and elevated lactate dehydrogenase levels. Non-HIV patients had longer treatment delays and higher hospitalization and mortality rates. Lymphopenia, steroid use, and pneumothorax were associated with 60-day mortality. The incidence of bacterial pneumonia in people living with HIV decreased, linked to improved CD4 counts. Children with HIV showed higher mortality from coronavirus-related pneumonia. CONCLUSIONS: Future research should expand epidemiological surveillance, explore new therapies, and investigate co-infections in at-risk groups, particularly children. Additionally, strengthening public health policies and promoting prevention education are essential to improve clinical outcomes in vulnerable populations.

Treatment with oclacitinib, a Janus kinase inhibitor, down-regulates and up-regulates CD25 and Foxp3 expression, respectively, in peripheral blood T cells of dogs with atopic dermatitis

BackgroundOclacitinib (OCL), a Janus kinase inhibitor, is a novel immunomodulatory/immunosuppressive agent which is an approved as the first-line treatment for atopic dermatitis (AD) in dogs. The aim of the study was to investigate the effects of OCL on CD4+ and CD8+ T cells and their selected subsets under clinical conditions, i.e. in dogs suffering from AD, in terms of both safety and immune mechanisms underlying its therapeutic actions. Eight dogs were treated for 28 days with OCL at the recommended dose. Blood samples were taken at day 0, 7, 14 and 28.ResultsThe study showed that the mean percentage and absolute count of CD4+ and CD8+ T cells on the 14th and 28th day of the treatment with OCL did not differ from the corresponding baseline values, i.e. those before the treatment. On the 7th day of the treatment, the mean absolute count of CD4+ T cells and the mean percentage and absolute count of CD8+ T cells were significantly increased. The research found that on the 14th day of the treatment, the mean percentage and absolute count of CD25+CD4+ and CD25+CD8+ T cells were significantly decreased; the reduction in the percentage of CD25+CD4+ T cells persisted on 28th day of the treatment. A two-week treatment with OCL resulted in an increase in the mean percentage of Foxp3+CD4+ T cells, and this effect was sustained at the last time point. The treatment with OCL decreased the eosinophil level but does not affect the absolute counts of basophils, monocytes and neutrophils.ConclusionsThe findings of the study strongly suggest that: (a) in terms of the impact of OCL on the number of PB CD4+ and CD8+ T cells, monthly treatment with the drug should be considered as a relatively safe; (b) the eosinophil-reducing effect and the down-regulation of the AD up-regulated CD25 expression on CD4+ Teff cells may constitute significant elements of the mechanism of action underlying the therapeutic effects of the drug in the treatment of canine AD; (c) the generation of inducible Foxp3-expressing CD4+ regulatory T cells - resulting in the shift of the CD4+ Treg cell (i.e. Foxp3+CD4+)/activated Teff (i.e. CD25+CD4+) cell balance toward an increased proportion of Treg cells - may be considered as additional mechanism involved in producing the immunomodulatory/immunosuppressive properties of OCL.

Prevalence of medication overload among older people with HIV: a MedSafer study

BackgroundOlder people with HIV (PWH) are at risk of polypharmacy (taking multiple medications). Most medications may be necessary and indicated to manage HIV (e.g., antiretroviral therapy [ART]) and HIV-associated comorbidities. However, some are potentially inappropriate medications (PIMs), defined as causing greater harm than benefit, which leads to medication overload. The objective of this study was to characterize polypharmacy (taking multiple medications) and medication overload (prescription of ≥ 1 PIMs) among older PWH.MethodsThis retrospective study included older PWH (aged ≥ 50 years old) attending the tertiary care HIV clinic at the McGill University Health Centre (Montreal, Canada), from June 2022–June 2023. Patient characteristics, medications, and select laboratory values (e.g., CD4 count, hemoglobin A1C) were entered into the MedSafer software identifying PIMs and classifying them according to risk of adverse drug event. We measured the prevalence of polypharmacy (≥ 5 medications prescribed, both including and excluding ART) and medication overload (≥ 1 PIMs). Multivariable logistic regression identified factors associated with medication overload.ResultsThe study included 100 patients, with a median age of 59 years (IQR = 54–63; range 50–82); 42% female. Polypharmacy affected 89% of patients when including antiretroviral therapy (ART) and 60% when excluding ART. Medication overload was present in 58% of patients, and 37.4% of identified PIMs were classified as high-risk. Polypharmacy was the sole predictor of medication overload.ConclusionOlder PWH are at significant risk of medication overload and receiving higher risk PIMs. Deprescribing PIMs in this population could improve medication appropriateness while reducing the risk of ADEs.

Magnitude of anemia and associated factors among HIV infected children on antiretroviral therapy in Awi zone health facilities, Northwest Ethiopia, 2023

BackgroundAnemia is a common complication of HIV infected children and it is enabling HIV disease progression, and decreasing survival. In Ethiopia, there is limited evidence on the prevalence of anemia and its associated factors among HIV infected children particularly in the Awi Zone. Therefore, this study aimed to assess the magnitude and associated factors of anemia among HIV infected children on ART aged from 6 months to 15 year-old in ART Clinic, Awi-Zone, Ethiopia.ObjectiveTo assess the magnitude and associated factors of anemia among HIV infected children on antiretroviral therapy in Awi zone health facilities, Northwest, Ethiopia, 2022.MethodsA facility based cross-sectional study design was conducted from October to December 2022. A simple random sampling method was used to select the study participants. Descriptive statistics, including frequencies and proportions was used to summarize the study variables and data had been entered in to Epi data 4.2 and exported to SPSS version 25. Bivariable logistic regression followed by multivariable logistic regression was performed. Degree of association between dependent and independent variables had been assessed using adjusted odds ratio with 95% CI at p value of ≤ 0.05.ResultFrom 346 participants in the selected sample 339 (97.9%) of them responded. Prevalence of anemia was 13.3% (n = 45) among which, majority (44.4%) of them had mild anemia, while about (42.2%,) had moderate anemia and around 13.3%, of them were severely anemic. Baseline CD4 count (AOR = 6.58, 95% CI: 2.85–15.22), WHO clinical stage III or IV (AOR = 8.42, 95% CI = 3.47, 20.45), hookworm infection (AOR = 5.06, 95% CI = 2.04, 12) and malaria infection (AOR = 4.92, 95% CI (2.19–11.02) were significantly associated with anemia among children on HAART.ConclusionThe prevalence of anemia among participants was relatively low in this study. However, a considerable proportion of participants had moderate to severe anemia. Lower CD4 count at enrolment, advanced HIV clinical stage, malaria and hookworm infection were significantly linked with anemia. Thus, it requires regular monitoring of anemia status in these patients for better clinical outcomes and quality of life improvements.

HIV replication and tuberculosis risk among people living with HIV in Europe: A multicohort analysis, 1983-2015.

HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.

Epigenetic associations with kidney disease in individuals of African ancestry with APOL1 high-risk genotypes and Human Immunodeficiency Virus.

Apolipoprotein L1 (APOL1) high-risk variants are major determinants of chronic kidney disease (CKD) in people of African ancestry. Previous studies have identified epigenetic changes in relation to kidney function and CKD, but not in individuals with APOL1 high-risk genotypes. We conducted an epigenome-wide analysis of CKD and estimated glomerular filtration rate (eGFR) in in people of African ancestry and APOL1 high-risk genotypes with HIV. DNA methylation profiles from peripheral blood mononuclear cells of 119 individuals with APOL1 high-risk genotypes (mean age 48 years, 49% female, median CD4 count 515 cells/mm3, 90% HIV-1 RNA <200 copies/mL, 23% with CKD) were obtained by Illumina MethylationEPIC BeadChip. Differential methylation analysis of CKD considered technical and biological covariates. We also assessed associations with eGFR. Replication was pursued in three independent multi-ancestry cohorts with and without HIV. DNA methylation levels at 14 regions were associated with CKD. The strongest signals were located in SCARB1, DNAJC5B and C4orf50. Seven of the 14 signals also associated with eGFR, and most showed evidence for a genetic basis. Four signals (in SCARB1, FRMD4A, CSRNP1 and RAB38) replicated in other cohorts, and 11 previously reported epigenetic signals for kidney function or CKD replicated in our cohort. We found no significant DNA methylation signals in, or near, the APOL1 promoter region. We report several novel as well as previously reported epigenetic associations with CKD and eGFR in individuals with HIV having APOL1 high-risk genotypes. Further investigation of pathways linking DNA methylation to APOL1 nephropathies is warranted.

Torque teno virus: a potential marker of immune reconstitution in youths with vertically acquired HIV

Torque teno virus (TTV) viral load (VL), a component of the human virome, increases during immune suppression or dysregulation. This study aimed to explore TTV VL in youths living with vertically acquired HIV (YWVH) and its potential as an immunovirological marker. We performed an observational, retrospective study involving YWVH under antiretroviral treatment (ART) from the Spanish Cohort of HIV-infected children, adolescents, and vertically HIV-infected patients transferred to Adult Units (CoRISpe-FARO), compared to HIV-negative healthy donors (HD). Plasma TTV VL was assessed by qPCR. T-cell phenotype was analysed on cryopreserved peripheral blood mononuclear cells by flow cytometry. Correlations with baseline CD4 and CD8 and long-term virological evolution were examined. A total of 57 YWVH were compared with 23 HD. YWVH had a median CD4 T-cells of 736 cells/mm3 [IQR: 574–906], a median of 17 years [IQR: 14–20.5] since ART initiation, and 65 months [IQR: 39–116] under HIV-RNA virological control. TTV VL was higher among YWVH and in males compared with females (p < 0.05). Among YWVH, TTV VL correlated with CD4 and CD8 counts and the CD4/CD8 ratio (p = 0.002; r = − 0.39, p = 0.037; r = 0.277, p = 0.005; r = − 0.37 respectively). TTV VL correlated with activation expression markers (HLA-DR+/CD38+) on CD4 (p = 0.007, r = 0.39) and the soluble proinflammatory cytokine IL-6 (p = 0.006, r = 0.38).

Mendelian Susceptibility to Mycobacterial Disease with Signal Peptide Peptidase-like 2A (SPPL2A) Deficiency: A Case Report

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by immunodeficiency, leading to increased susceptibility to mycobacterial infections. Studies have identified several genes that are associated with MSMD in the interferon-gamma/interleukin (IL)-12/IL-23 signaling pathway. One of these genes is signal peptide peptidase-like 2A (SPPL2A), which is very rare, and defects in this gene have been reported only in 3 patients with MSMD. This case report presents the rare SPPL2A deficiency with an abnormal presentation, which adds to the limited number of these genetic defects. This report presents the case of a 1-year-old boy who developed Bacillus Calmette-Guerin infection (BCGitis), lymphadenopathy, and an arm abscess that required surgical drainage following BCG vaccination. The patient had hypogammaglobulinemia, normal B-cell counts, normal CD4 counts, low CD8 counts, and SPPL2A deficiency, which is related to MSMD. The patient received a second line of anti-tuberculosis agents. SPPL2A deficiency is associated with MSMD and can cause severe BCGitis and disruption of immunoglobulin production.

Correlation between elderly patients with COPD and the impact on immunity in tuberculosis patients: A retrospective study.

The prevalence of chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) is increasing globally, yet their comprehensive impact on the immune system remains underexplored. This study aimed to provide a thorough assessment of the immune status of patients with COPD and tuberculosis (TB-COPD), including their pulmonary conditions, immune cell responses, and changes in lymphocyte subpopulations. A total of 151 patients with TB-COPD patients were included, and clinical data were compared between the TB-COPD group and a group of TB patients without COPD (TB-NCOPD). Lung imaging findings and peripheral blood immune cell levels were compared between the 2 groups. Flow cytometry was used to analyze the absolute counts of lymphocyte subpopulations. The incidence of pulmonary lobe lesions and cavitation in the TB-COPD group aged 70 years or older was significantly higher than that in the control group. At the immune cell level, patients with TB-COPD showed a significant reduction in total lymphocytes, CD4+ T lymphocytes and CD4+/CD8+ ratio. Regardless of COPD status, the CD4+ T cell count in the CMV-infected group was significantly lower than that in the uninfected group (P < .05). Additionally, the CD4+/CD8+ ratio in the COPD + TB CMV + group was significantly lower than that in the uninfected group. Analysis of lymphocyte subpopulations revealed a decrease in the counts of CD4+ T lymphocytes in patients with TB-COPD, potentially associated with the chronic inflammatory state induced by COPD. The one-month treatment outcomes showed that the improvement rate in the control group was 70.58%, which was significantly higher than the 38.92% in the COPD + TB group (P < .001). We observed a significant increase in the number of pulmonary cavity patients in the TB-COPD group, suggesting that COPD may be a potential risk factor for the formation of pulmonary cavities in patients with TB. At the immune cell level, TB-COPD patients showed a notable decrease in lymphocytes and CD4+ T lymphocytes, implying that COPD combined with pulmonary TB may significantly affect the immune system, leading to a reduction in the counts of key immune cells.

The impact of prebiotic, probiotic, and synbiotic supplements on CD4, CD8 counts and inflammatory markers in HIV patients: A systematic review and meta-analysis

The impact of prebiotic, probiotic, and synbiotic supplements on CD4, CD8 counts and inflammatory markers in HIV patients: A systematic review and meta-analysis

Mpox and Lessons Learned in the Light of the Recent Outbreak: A Narrative Review.

According to the WHO, more than 90,000 cases of mpox have been reported since the 2022 worldwide outbreak, which resulted in 167 deaths, while a new outbreak in Africa since 2023 has resulted in over 18,000 cases and 617 deaths. Mpox is a zoonosis caused by the monkeypox virus, a double-stranded DNA virus belonging to the Orthopoxvirus genus, which causes smallpox-like illness. Until 2022, cases were predominately located in West and Central Africa, with only sporadic cases and outbreaks reported in other parts of the world. During the 2022 outbreak, the primary mode of transmission was sexual contact among men who have sex with men. The changing epidemiology of mpox resulted in new disease phenotypes and populations at risk, disproportionally affecting people who live with HIV. Commonly presenting as a mild, self-limiting illness, mpox can cause severe and protracted disease in people with HIV with a CD4 count < 200 cell/mm3. The global emergence of mpox that followed and intersected with COVID-19 mobilized the scientific community and healthcare stakeholders to provide accurate diagnostics, preventive vaccines and treatment to those most affected. Despite existing gaps, this rapid response helped to contain the outbreak, but challenges remain as new variants emerge. Preparedness and readiness to respond to the next outbreak is crucial in order to minimize the impact to the most vulnerable.

Optimizing Patient Care through Analysis of HIV-1 Genotyping: Insights into Test Ordering Strategies, Clinical Relevance, and Implications for Managing Drug Resistance

Abstract Background Antiretroviral resistance can lead to treatment failure and disease progression, especially in HIV patients. HIV-1 sequencing/genotyping tests (e.g., GenoSure) can be ordered by clinicians to detect HIV drug resistance (HIVDR). Here, we investigated our institution’s ordering practices, clinical relevance, and rates of HIVDR. Methods A total of 94 patients positive for HIV-1 between 01/2019-08/2021 were included (n=46 pre-COVID-19 prior to 03/11/2020; n=48 post-COVID-19). Patients’ charts were reviewed for demographics, laboratory results, clinical presentation, and antiviral management. Student t-test and Fisher exact test were used for statistical analyses. Results HIV-1 genotyping was ordered most by Medicine (67%), Surgery, (7%), Emergency medicine (6%), Neurology and Obstetrics &amp; Gynecology (5% each). Only 70% of patients with GenoSure ordered and sent out had sufficient viral loads for genotyping. Among the patients with insufficient viral loads, the GenoSure test was most ordered by Medicine (68%), Surgery (9%) and Ob/Gyn (9%) departments. Our HIV patient population was predominantly male (70%) and had a mean age of 49 years (range: 25 to 90 years). Lower viral loads (1.8x105 vs. 3.4x105 copies/mL, p=0.05), CD4 counts (174 vs. 196 cells/mcL, p=0.7), CD8 counts (555 vs. 800 cells/mcL, p=0.04), and higher CD4/CD8 ratio (0.312 vs. 0.266, p=0.57) were seen in our post-COVID-19 patients. The overall prevalence of HIVDR was 20%. There was a 9% increase in HIVDR, predominantly in non-nucleotide reverse transcriptase inhibitors (NNRTI), after the COVID-19 pandemic. For example, higher resistance was documented for antiviral drugs Efavirenz (16%), Nevirapine (16%), and Rilpivirine (13%). Increased prevalence of mutations in G190A, K101, K103, and E138 positions which confer resistance to NNRTIs was seen. The GenoSure test results helped optimize antiviral therapy in 47.8% (42/88) of total cases, with an increase of 12.5% in patients from post-COVID-19 era. Infectious disease consultations led to more actionable changes (16% increase) and ordering of the updated version of the GenoSure test that includes integrase inhibitors (20% increase, p=0.005). Conclusion We have implemented stringent clinical criteria including pathologist approval and changed our electronic health record ordering system to ensure GenoSure is appropriately ordered. Diagnostic stewardship of sequencing tests needs to be implemented to ensure actionable clinical changes in the right patient population and to control testing costs. Additionally, our findings revealed increased HIVDR in our patient population post-COVID-19. Continued surveillance and collaboration with antimicrobial stewardship are critical to managing HIVDR and improving patient outcomes, particularly given the significant strain that the COVID-19 pandemic has placed on our healthcare system.

Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad® (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases.

Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8+ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

Evaluation of CMV T-cell Mediated Immunity in Children with CMV DNAemia After Allogeneic Hematopoietic Cell Transplantation

Abstract Background Cytomegalovirus (CMV) is among the most common infectious complications following allogeneic hematopoietic cell transplantation (allo-HCT). A commercially available CMV T-cell immune panel (CMV-TCIP, Viracor®), reported as percentages of CMV-specific interferon gamma releasing CD4 and CD8 cells (%CMV-CD4 or %CMV-CD8 IFN-γ), may be used to assess CMV cell-mediated immunity (CMV-CMI). However, the utility of this assay among pediatric allo-HCT recipients remains unknown. Methods A retrospective analysis among pediatric allo-HCT recipients (age ≤18 years) from 1/2020 to 11/2023 who developed CMV DNAemia and had CMV-TCIP testing was performed. Per institutional protocol, weekly quantitative plasma CMV PCR was performed until day +100. Clinically significant CMV infection (csCMVi) was defined as CMV viral load (VL) ≥500IU/ml and pre-emptive therapy (PET) was provided for csCMVi. The most frequent indications for CMV-TCIP testing were to evaluate CMV-CMI to inform the need of CMV virus-specific T-cell therapy (CMV-VST) in the setting of resistant/refractory CMV, to monitor CMV-CMI as a proxy of VST expansion post CMV-VST, or to evaluate the need of ongoing secondary antiviral prophylaxis. A %CMV-CD4 or %CMV-CD8 IFN-γ ≤0.2% was categorized as a poor response, whereas a result &amp;gt;0.2% was classified as an adequate response. Specimens with insufficient quality, high background, or discrepant results from %CMV-CD4 or %CMV-CD8 were classified as a discordant response. Demographics, underlying condition, HCT type, conditioning regimen, antiviral agents and use of VST, VL, and CMV-TCIP results were recorded. Descriptive and nonparametric statistics (median, interquartile range [IQR]) were used for analysis. Results Twenty-seven CMV-TCIP results from 10 unique allo-HCT recipients were analyzed. The median age at transplant was 8.5 years (IQR 2.75-14.3), predominantly for hematologic malignancy (70%). CMV donor/recipient (D/R) serostatus were D+/R+ (60%), D-/R+ (30%) and D+/R- (10%). CMV DNAemia developed post-HCT in 80% (8/10) with median onset of 4 days post-HCT (IQR 3-40) and 2 subjects had known DNAemia prior to HCT. Nine (90%) subjects were started on PET for csCMVi, whereas 1 (10%) received antiviral therapy when VL was &amp;lt;500IU/ml. The first CMV-TCIP was obtained at median of 112 days (IQR 42-130) post-HCT. Despite appropriate antiviral therapy, patients with a peak VL ≥500 IU/mL (obtained within 1 week before and after CMV-TCIP testing) demonstrated significantly lower absolute CD4 (median 12 vs. 198 cells/uL, p=0.02) and CD8 (median 79 vs. 443 cells/uL, p=0.04) counts and %CMV-CD4 IFN-γ (0.04% vs. 0.36%, p=0.02) compared to those with a peak VL &amp;lt;500 IU/mL. Conclusion Our results suggest that CMV-CMI, particularly %CMV-CD4 IFN-γ &amp;gt;0.2%, was observed concurrently with downward trending VL, and may serve as a proxy of VST expansion in patients receiving CMV-VSTs. Figure 1A. The distribution of peak VLs over time based on %CMV-CD4 and %CMV-CD8 IFN-γ are demonstrated in Figure 1B. CMV peak VLs were lower with TCIP testing results reported as adequate combined responses compared to those with poor combined responses. In five subjects (50%) who received CMV-VSTs as part of CMV therapy, increased %CMV-CD4 and %CMV-CD8 IFN-γ were observed post-infusion with an observed downward trend in VL.

The prevalence of Tuberculosis in HIV patients and their correlation with CD4+ count in a tertiary care hospital in Rishikesh, gateway to the Himalayas

IntroductionTuberculosis is the most common serious opportunistic infection in HIV-positive patients. TB can occur at any time during the course of HIV infection. The estimated number of people living with HIV in India in 2019 was 23.48 lakh. With an estimated 2.5 million cases, or 195 cases per 1 lakh people, India has the highest incidence of tuberculosis cases worldwide, accounting for about 23% of all cases, according to MOHFW India. Information about HIV/TB co-infection is still scarce in India, especially in the hilly areas of Uttarakhand. Material and methodsIn this retrospective study, subjects are the patients who are diagnosed with MTB in HIV-positive patients of all age groups and sex and were followed up from January 2021 till August 2022 in a tertiary referral hospital AIIMS Rishikesh.Diagnosis of MTB was based on clinical, laboratory, and neuroimaging signs, and HIV was based on dot blot, immunochromatographic, and chemiluminescence assay. ResultA total of 520 patients screened for HIV were positive. Out of which 145 were MTB in which 133 had pulmonary tuberculosis and 12 had extra-pulmonary tuberculosis. The patients' average age was 35.5 years. Among males, females and transgender, 97 (66.89%), 46 (31.72%) and 2 (1.38%) have both TB and HIV co-infections respectively.Mean CD4 count prior to ATT was 350.21, After completion was 486.48. The prevalence of Tuberculosis among HIV positive cases was 23.8%.Baseline and latest CD4 count was conducted before and after ART and ATT treatment. It was observed that there was significant increase in the CD4 count after treatment. ConclusionHIV co-infection with TB is higher in this region. There is a role of CD4+ count in the prognosis and progression of the disease. More strategic measures are required for early diagnosis and treatment of HIV to combat MTB.