Human Immunodeficiency Virus Infection Research Articles

Tumor Initiation and Progression in People Living on Antiretroviral Therapies

Antiretroviral therapy (ART) has significantly extended the lifespan of people living with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS), thereby transforming the disease into a manageable chronic condition. However, this increased longevity has led to a higher incidence of non-AIDS-defining cancers (NADCs) among this population. In this holistic review, we explore the complex interactions between HIV, ART, and cancer development, focusing on how ART influences tumor initiation and progression in people living with HIV/AIDS (PLWHA). Our findings from this reveal several critical aspects of cancer risk in PLWHA. Firstly, while ART restores immune function, it does not fully normalize it. Chronic immune activation and persistent inflammation continue to be prevalent, creating a conducive environment for oncogenesis. Additionally, PLWHA are more susceptible to persistent infections with oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV), further increasing cancer risk. Some ART drugs have been implicated in genotoxicity and mitochondrial dysfunction, potentially promoting tumorigenesis. ART-induced metabolic changes, including insulin resistance and dyslipidemia, are also associated with heightened cancer risk. Common NADCs in PLWHA include lung cancer, liver cancer, anal cancer, and Hodgkin lymphoma, each with distinct etiologies linked to both HIV-related and ART-related factors. The interplay between HIV infection, chronic inflammation, immune restoration via ART, and the direct effects of ART drugs creates a unique cancer risk profile in PLWHA. Although ART reduces the incidence of AIDS-defining cancers, it does not confer the same protective effect against NADCs. Persistent HIV-related inflammation and immune activation, despite viral suppression, are key factors in cancer development. Additionally, long-term exposure to ART may introduce new oncogenic risks. These insights highlight the need for integrated cancer screening and prevention strategies tailored to PLWHA. Future research is needed to focus on identifying biomarkers for early cancer detection and developing ART regimens with lower oncogenic potential. Healthcare providers should be vigilant in monitoring PLWHA for cancer and adopt comprehensive screening protocols to mitigate the increased cancer risk associated with ART.

End tuberculosis strategy also requires initiation and integration of a national silicosis control program with the ongoing tuberculosis elimination activities: A review of the silicotuberculosis situation in India

Background: Earlier studies conducted by Indian researchers have demonstrated that the elimination of tuberculosis (TB) requires proactive control of silicosis, given India’s significant burden of silicosis and its common comorbidity, pulmonary TB, also known as silicotuberculosis. The TB Control Indian Health Authority saw human immunodeficiency virus infection, diabetes, and malnutrition, among others, as important risk factors for case findings, but overlooked the significance of silicosis. Silicotuberculosis control is often confronted with challenges of detecting microorganisms, uncertain treatment outcomes, a higher likelihood of mono-drug and multi-drug resistance, and increased mortality due to treatment failure. In addition, silicosis has a long latent period, typically 15 years or more, from the onset of silica dust exposure to the appearance of opacities on radiological examination, which is the conventional method of diagnosis of the condition. Objective and recommendation: Facing the aforementioned situation, scientists of the Indian Council of Medical Research-National Institute of Occupational Health have identified a useful biomarker, Club cell secretory protein 16 (CC-16) (a lung protein), that might serve as a surrogate marker for early detection of silicosis among silica dust-exposed workers. An added benefit of CC-16 is its ability to detect sub-radiological silicosis, which is recognized as a risk factor for TB and multi-drug-resistant TB. At present, two researchers have developed point-of-care devices for detecting silica-dust-induced lung damage using serum CC-16, to support its further application. Conclusion: The present review highlights possible mechanisms for the early detection of silicosis and silicotuberculosis by assessing several relevant research publications, and the findings suggest that a national silicosis control program, to be integrated with existing TB elimination activities for sustainable and improved outcomes, should be initiated.

Understanding depression, anxiety and stress in young people living with HIV in Ghana

Ghanaians with perinatally acquired human immunodeficiency virus (HIV) infection now live into adulthood. It is known that adolescents and young adults living with HIV have a high risk of mental health comorbidity. Despite increasing global attention on HIV–mental health interactions, the field remains understudied in Ghana, with an attendant lack of national integrated care solutions. This study aimed to measure the burden and explore the context of depression, anxiety and stress symptoms among young people living with HIV receiving care at a tertiary care hospital in Ghana. This was an explanatory sequential mixed-methods study. Depression, anxiety and stress symptoms were measured using the Depression, Anxiety and Stress Scale, and their associations with quality of life (QoL), socioeconomic status, internalised stigma, disease stage and HIV-related risk-taking behaviours were explored. After preliminary quantitative data analysis, semi-structured interviews were conducted for those who screened positive for depression and/or anxiety to explore their experience with this comorbidity. This study found a low prevalence of depression and anxiety symptoms, which were associated with higher stigma scores and lower QoL. We believe this low prevalence to be attributable to the effect of several psychosocial interventional programmes, which were previously piloted with the study cohort that have gradually normalised mental health discussions. Participants also showed marked resilience and knowledge about their condition. The results of this study present an opportunity to advocate and scale up effective locally adapted and strength-based solutions to address the mental illness–HIV syndemic in Ghanaian young people living with HIV.

A cGAS-mediated type I interferon response in human CD4+ T cells depends on productive infection and is conserved over HIV types and strains.

Human immunodeficiency virus (HIV) type 2 is known to be less pathogenic than HIV-1, possibly due to more effective immune control mechanisms. The mechanism of innate sensing of HIV-2 by T cells is at present unclear. In this study, we show that several primary isolates of HIV-2 (CBL20 and CI85) and HIV-1 (A8 and D2), similar to the molecular clone HIV-1 NL4.3-GFP-I, induce a significant type I interferon response in its main target, activated CD4+ T cells. However, they are unable to do so after shRNA-mediated knock-down of cGAS. In addition, both HIV-1- and HIV-2-induced type I interferon response in CD4+ T cells was dependent on productive infection and integration, as the presence of RT or integrase inhibitor dramatically suppressed the sensing. Our findings collectively showed that the cGAS-dependent type I interferon response of CD4+ T cells to HIV infection is conserved over HIV types and critically depends on productive infection.IMPORTANCEBy unveiling the role of cGAS in sensing Human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) across CD4+ T cells and highlighting its broader relevance that might be mirrored in other cell types, our research provides insights into the uniform mechanism of innate immune activation by different HIV isolates. By demonstrating the necessity of productive infection, we highlight the robust and specific nature of the observed cGAS-mediated innate response, dispelling concerns about contaminating plasmids triggering an immune response. Our preliminary data suggest that the lower pathogenicity of HIV-2 may not be directly correlated to superior innate immune control mediated by cGAS.

Analyzing Knowledge Status and HIV Linkage to Care: Insights From America's HIV Epidemic Analysis Dashboard (AHEAD) National Database.

Understanding knowledge of human immunodeficiency virus (HIV) status and timely linkage to care are crucial for improving health outcomes among individuals living with HIV. This study analyzes trends in HIV knowledge status and linkage to care using data from America's HIV Epidemic Analysis Dashboard (AHEAD) National Database. A retrospective database analysis was conducted utilizing the AHEAD National Database, focusing on individuals diagnosed with HIV from 2017 to 2022. Key variables included knowledge of HIV status and the percentage of individuals who received medical care within one month of diagnosis. Descriptive statistics were employed to assess trends over the years, while demographic differences were analyzed based on age, gender, race, and transmission risk. The incidence of new HIV infections in the United States has gradually declined from 37,000 in 2017 to 31,800 in 2022. Between 2017 and 2022, the percentage of people with HIV receiving medical care within one month of diagnosis increased from 77.80% to 81.60%. The actual number of individuals linked to care peaked at 27,479 in 2019 but dropped to 23,419 in 2020. However, by 2022, the number had risen to 29,753, reflecting improvements in linkage efforts. Additionally, the number of individuals aware of their positive HIV status increased from 988,546 in 2017 to 1,079,751 in 2022, with the estimated percentage reaching 87.20%. Although this indicates progress in awareness initiatives, the increase remains gradual. Disparities in care linkage across demographics, particularly among younger individuals and racial minorities, highlight the need for targeted interventions to improve overall outcomes and access to care. The findings highlight significant progress in knowledge status and linkage to care among people living with HIV. Despite improvements, achieving the goal of 95% linkage to care by 2025 remains a challenge, particularly for specific demographic groups. Enhanced public health strategies and targeted outreach efforts are essential for addressing these disparities and improving overall health outcomes.

Factors associated with positive human papillomavirus (HPV) test results in cervical precancer screening: a cross-sectional study at Souro Sanou National Teaching Hospital (SSNTH) in Bobo Dioulasso, Burkina Faso.

Human papilloma virus testing is a new method of screening for precancerous cervical lesions. Here we identified factors associated to the positive Human papilloma virus-testing in the context of cervical precancer screening at the Souro Sanou National Teaching Hospital in Burkina Faso. Conducted from June 2021-May 2022, this was a cross-sectional study, including patients aged between 25 and 55years-old and screened for precancerous lesions and received HPV-testing at the Department of Gynecology, Obstetrics and Reproductive Medicine (DGORM) of the SSNTH. The proportion of positive HPV-test was calculated, and we identified factors associated to positive HPV-test using logistic regression. Of the 759 patients came for precancerous lesions screening, 559 patients were included. Their mean-age was 38.8 ± 7.9years-old, 94.3% were from urban area and 50.3% identified as housewives. Regarding the past medical history, it noted: number of gestures (3.2 ± 2.0), parity (2.8 ± 1.9), number of living children (2.8 ± 1.9), having abortion experience (24.0%), age of first-sexual-intercourse(18.6 ± 2.3years), alcohol (9.1%) and tobacco (1.0%) consumption, sexually-transmitted-infection (27.0%), Human immunodeficiency virus (HIV)infection (5.0%); none had been vaccinated against HPV. Biologically, 16.6% [95% CI: 13.6-20] of the women had a positive HPV-test. The factors significantly associated with positive HPV-test were: occupation in the private sector [OR: 0.06(0.0-0.5); p < 0.001], having a sexually-transmitted-infection [OR: 3.9(2.0-7.7); p < 0.001], age of first-sexual-intercourse [OR: 0.7(0.6-0.9); p < 0.001], sexual-multiple-partnership [OR: 17.5(8.1-39.6); p < 0.001], and HIV status [OR: 13.2(4.4-40.5); p < 0.001]. These results call for health actions through the reinforcement for behavioral change mainly about sexually-transmitted-infections, and for the raising awareness of the population for the screening related to the precancerous lesions and HIV.

An analytical observational study for diagnostic accuracy of volume, conductivity & scatter (VCS) indices of neutrophils for diagnosis of sepsis in an emergency hospital setting.

Background & objectives The newer technique using an innovative volume conductivity scatter (VCS) technology is emerging as a surrogate for sepsis diagnosis. The VCS technology offers a more objective method to measure cell volume (V), characterize conductivity (C) and light scatter (S) directly from more than 8,000 white blood cells (WBCs). However, diagnostic performance of VCS parameters in sepsis has not been extensively tested in routine hospital emergency settings. Therefore, the present study aimed to investigate the diagnostic and prognostic performance of VCS markers of neutrophils in our local hospital emergency setting. Methods It was an observational analytical study with 41 cases of sepsis and 43 healthy controls aged above 18 yr. Individuals with acute coronary syndrome and individuals with already diagnosed Human Immunodeficiency Virus (HIV) infection were excluded from the study. Results The mean neutrophil volume (MNV) values were not significantly different between cases and controls (P 0.138) whereas mean neutrophil conductance (MNC) and mean neutrophil scatter (MNS) measurements were significantly higher among cases as compared to controls (both P-values <0.001). According to Receiver Operating Characteristics (ROCs) curve analysis, MNV in our study failed to show statistically significant discriminatory ability in sepsis (AUC 0.54) whereas MNC (AUC 0.98) and MNS (AUC 0.95) showed marked discriminatory ability in diagnosing sepsis in this study cohort. Interpretation & conclusions Among VCS parameters, MNV failed as a standalone biomarker of sepsis in routine emergency setting whereas MNC and MNS had statistically significant diagnostic and discriminatory accuracies among hospitalized affected individuals with sepsis.

Next-Generation Sequencing Methods for Near-Real-Time Molecular Epidemiology of HIV and HCV.

The World Health Organisation has set targets of reducing the transmission of new hepatitis C (HCV) infections by 90%, and ending human immunodeficiency virus-1 (HIV) as a public health threat, by 2030. To achieve this, efficient and timely viral surveillance, and effective public health interventions, are required. Traditional epidemiological methods are largely dependent on the recognition of incident cases with symptomatic illness; acute HIV and HCV infections are commonly asymptomatic, which may lead to delays in the recognition of such new infections. Instead, for these viruses, molecular epidemiology may improve the detection of, and response to, clusters of viral transmission. Molecular epidemiology using historical datasets has highlighted key populations that may have benefitted from a timely intervention. Similar analyses performed on contemporary samples are needed to underpin the 2030 targets, but this requires the generation of a cohesive dataset of viral genome sequences in near-real-time. To generate such data, methodologies harnessing next-generation sequencing (NGS) should be utilised. Here we discuss the opportunity presented by NGS for public health surveillance of HIV and HCV, and discuss three methods that can generate sequences for such analysis. These include full-length genome amplification, utilised for analysis of HCV in the research space; tiling PCR, which was the method of choice for many diagnostic laboratories in the SARS-CoV-2 pandemic; and bait-capture hybridisation, which has been utilised in local HIV outbreaks. These techniques could be applied for near-real-time HIV and HCV surveillance, informing public health strategies that will be key to achieving 2030 targets.

Pregnancy-associated de novo systemic lupus erythematosus in people living with HIV/AIDS

Abstract Pregnancy with systemic lupus erythematosus (SLE) requires special attention in view of the enhanced risks to the fetus and the aggravation of SLE during pregnancy. Human immunodeficiency virus infection can further complicate the course of pregnancy as well as the outcome. We present a case of a 28-year-old primigravida who was diagnosed case of people living with HIV/AIDS and presented with SLE at 34 weeks of gestation. Subsequent evaluation of the patient revealed latent tuberculosis also. Cutaneous lesions responded well to oral corticosteroids, however, the outcome of pregnancy was hydrops fetalis. This report highlights the complex interplay of multiple comorbidities and their adverse impact on pregnancy outcome.

Epidemiologic characteristics of people living with human immunodeficiency virus in South Korea: a nationwide cohort study

Recent information regarding the characteristics of people living with human immunodeficiency virus (HIV) (PLWH) is lacking. Therefore, we examined the incidence of HIV infection and epidemiologic characteristics of PLWH in South Korea using recent National Health Insurance Service database data. The HIV infection rate was 4.13 per 100,000 in 2017, 4.19 per 100,000 in 2018, 6.61 per 100,000 in 2019, 5.98 per 100,000 in 2020, 8.81 per 100,000 in 2021, and 4.14 per 100,000 in 2022. In 2016, the mean age of PLWH was 45.7 years (SD: 13.8 years), and it gradually increased to 49.0 years (standard deviation: 13.7 years) in 2022 over 7 years in South Korea. The proportion of male individuals among PLWH was 90.7% (19,970/22,026) in 2016, and it gradually increased to 92.3% (22,943/24,857) in 2022 over 7 years in South Korea. The proportion of anti-retroviral therapy (ART) users among PLWH in South Korea was 92.6% (20,388/22,026) in 2016, and it gradually increased to 97.9% (24,328/24,857) in 2022 over 7 years. In this population-based cohort analysis, we presented the HIV infection incidence and epidemiologic features of PLWH in South Korea. This study’s results may influence future infection prevention strategies and policies for PLWH.

Assessment of Some Micronutrients and Vitamins of HIV Positive Patients in South-South Nigeria

Background: Human Immunodeficiency Virus (HIV) infection continues to be a serious health issue in most parts of the world, with a global prevalence of 0.7% among adults, the majority being in developing countries with limited healthcare resources. Objective: The objectives of this study was to determine the Iron, calcium, zinc, copper, Vitamins D and B12 of HIV positive subjects compared with the control, with respect to gender, age and with respect to duration of treatment. Materials: A total of fifty (50) HIV-positive subjects and fifty (50) HIV-negative subjects (control) were used in this study. Zinc, iron and calcium were evaluated using atomic absorption spectrophotometer, Vitamins D and B12 was done using ELISA, while calcium was estimated using O-cresolphthalein complexone method. The results were presented in tables and chart as mean ± standard deviation. Statistical analysis was done using one way Analysis of Variance (ANOVA) and Student’s t-test using Statistical Package for Social Sciences (SPSS) version 21.0. A p-value of &lt;0.05 was considered significant. Results: Among the study population, 23 (46.0%) were males and 27 (54.0%) were females. With respect to age, 29 (58.0%) were aged 20 – 40 years, while 21 (42.0%) were aged 41 years and above. Based on treatment period, 28 (56.0%) were less than one year, while 22 (44.0%) were more than one year. Among the control subjects, 32 (64.0%) were males and 18 (36.0%) were females. With respect to age, 24 (48.0%) belonged to age group 20 – 40 years, while 26 (52.0%) belonged to age group 41 years and above. The results obtained showed that Calcium, zinc, copper, Iron, Vitamins B12 and D were significantly lower in HIV positive subjects compared with control (p&lt;0.05). Calcium, Iron, Vitamins B12 and D were significantly lower (p&lt;0.05) in age group 41 years and above in comparison with age group 20 – 40 years. Calcium, Iron, Vitamins B12 and D were significantly (p&lt;0.05) higher in HIV positive subjects undergoing treatment for over a year compared with those undergoing treatment for less than one year. There was a significant positive correlation between Calcium and Iron (r=0.840, p=0.000), Calcium and Vitamin B12 (r=0.744, p=0.000), Calcium and Vitamin D (r=0.825, p=0.000), Iron and Vitamin B12 (r=0.743, p=0.000), Iron and Vitamin D (r=0.765, p=0.000) and Vitamin B12 and Vitamin D (r=0.562, p=0.000). Conclusion: The study concludes that the decrease in vitamins and micronutrients that accompanies HIV infection suggests a potentially important role of nutritional supplementation and good nutrition in the proper management of HIV/AIDS.

Analysis of the expression characteristics and clinical value of immune function indicators in patients with human immunodeficiency virus infection.

To explore the expression characteristics and clinical value of immune function indicators in patients with human immunodeficiency virus (HIV) infection. In this retrospective study, clinical data of 196 patients with HIV infection (observation group) and 196 health examinees (control group) admitted to our hospital from November 2021 to March 2023 were retrospectively analyzed. Patients in the observation group were further classified based on the staging as acute phase (n=53), asymptomatic phase (n=65), and acquired immunodeficiency (AIDS) phase (n=78). Levels of immune function indicators in the observation group and the control group were compared, and the correlation between immune function index levels and disease staging was analyzed. Levels of CD3+, CD4+, CD4+/CD8+, B cells, and NK cells were lower in the observation group (P<0.05), were significantly lower in asymptomatic patients compared with patients in the acute phase (P<0.05), and were significantly lower in patients with AIDS than those in asymptomatic patients (P<0.05). The results for CD8+ were in contrast to the above(P<0.05). Spearman analysis confirmed that levels of CD3+, CD4+, CD4+/CD8+, B cells and NK cells significantly negatively correlated, and levels of CD8+ significantly positively correlated with the stages of HIV (P<0.05). The immune function indicators of patients with HIV infection are markedly abnormal, which is mainly manifested by the decreased levels of CD3+, CD4+, CD4+/CD8+, B cells and NK cells, and the increased levels of CD8+. The profile of the immune function indicators correlates with the progressive severity of the disease.

Abnormal spirometric patterns and respiratory symptoms in HIV patients with no recent pulmonary infection in a periurban hospital in Ghana.

Human immunodeficiency virus (HIV) infection is associated with chronic airway obstruction, even in patients who have achieved viral suppression from combination antiretroviral treatment (cART). Spirometry is a supplementary test that aids in diagnosing pulmonary dysfunction in people living with HIV. To compare the prevalence of spirometric abnormalities among cART-treated HIV patients and cART-naïve HIV patients with non-HIV controls with no recent history of pulmonary infection in a peri-urban hospital in Ghana. In a case-control design, spirometry was performed in 158 cART-treated HIV patients, 150 cART-naïve HIV patients and 156 non-HIV controls. Clinical, sociodemographic data and respiratory symptoms were collected using a structured questionnaire. Spirometric abnormalities were categorised as obstructive (OSP) or restrictive (RSP) spirometric patterns based on the Cameroonian reference equation. The prevalence of OSP was higher in the cART-treated and cART-naïve HIV patients compared to non-HIV controls (13.9% vs 10.7% vs 5.1% respectively, p = 0.026), whereas that of RSP was similar among the study groups. Respiratory symptoms were common among cART-treated and cART-naïve HIV patients compared to non-HIV controls (48.1% vs 40% vs 19.2% respectively, p < 0.001). The major factors associated with OSP were female gender [OR (95% CI) = 2.46 (1.09-5.13), p = 0.031], former cigarette smoking [1.92 (1.04-3.89), p < 0.001], exposure to medium-to-high levels of biomass [3.07 (1.16-8.73), p = 0.019], presence of a respiratory symptom [1.89 (1.11-5.08), p = 0.029] and unemployment [3.26 (1.19-8.95), p = 0.042]. The major determinants of RSP were age, female gender [1.74 (1.05-4.29), p = 0.041], former cigarette smoking [2.31 (1.27-6.77), p < 0.001] and medium-to-high biomass exposure [1.58 (1.06-5.37), p = 0.043]. In HIV patients without any recent pulmonary infection in a peri-urban area of Ghana, there was a higher prevalence of OSP among cART-treated and cART naïve HIV patients compared to the non-HIV control. However, the prevalence of RSP was similar among HIV patients and non-HIV controls.

Minimally Modified HIV-1 Infection of Macaques: Development, Utility, and Limitations of Current Models.

Nonhuman primate (NHP) studies that utilize simian immunodeficiency virus (SIV) to model human immunodeficiency virus (HIV-1) infection have proven to be powerful, highly informative research tools. However, there are substantial differences between SIV and HIV-1. Accordingly, there are numerous research questions for which SIV-based models are not well suited, including studies of certain aspects of basic HIV-1 biology, and pre-clinical evaluations of many proposed HIV-1 treatment, prevention, and vaccination strategies. To overcome these limitations of NHP models of HIV-1 infection, several groups have pursued the derivation of a minimally modified HIV-1 (mmHIV-1) capable of establishing pathogenic infection in macaques that authentically recapitulates key features of HIV-1 in humans. These efforts have focused on three complementary objectives: (1) engineering HIV-1 to circumvent species-specific cellular restriction factors that otherwise potently inhibit HIV-1 in macaques, (2) introduction of a C chemokine receptor type 5 (CCR5)-tropic envelope, ideally that can efficiently engage macaque CD4, and (3) correction of gene expression defects inadvertently introduced during viral genome manipulations. While some progress has been made toward development of mmHIV-1 variants for use in each of the three macaque species (pigtail, cynomolgus, and rhesus), model development progress has been most promising in pigtail macaques (PTMs), which do not express an HIV-1-restricting tripartite motif-containing protein 5 α (TRIM5α). In our work, we have derived a CCR5-tropic mmHIV-1 clone designated stHIV-A19 that comprises 94% HIV-1 genome sequence and replicates to high acute-phase titers in PTMs. In animals treated with a cell-depleting CD8α antibody at the time of infection, stHIV-A19 maintains chronically elevated plasma viral loads with progressive CD4+ T-cell loss and the development of acquired immune-deficiency syndrome (AIDS)-defining clinical endpoints. However, in the absence of CD8α+ cell depletion, no mmHIV-1 model has yet displayed high levels of chronic viremia or AIDS-like pathogenesis. Here, we review mmHIV-1 development approaches, the phenotypes, features, limitations, and potential utility of currently available mmHIV-1s, and propose future directions to further advance these models.

Investigating the impact of stochasticity on HIV infection dynamics in CD4+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{+}$$\\end{document} T cells using a reaction-diffusion model

The disease dynamics affect the human life. When one person is affected with a disease and if it is not treated well, it can weaken the immune system of the body. Human Immunodeficiency Virus (HIV) is a virus that attacks the immune system, of the body which is the defense line against diseases. If it is not treated well then HIV progresses to its advanced stages and it is known as Acquired Immunodeficiency Syndrome (AIDS). HIV is typically a disease that can transferred from one person to another in several ways such as through blood, breastfeeding, sharing needles or syringes, and many others. So, the need of the hour is to consider such important disease dynamics and that will help mankind to save them from such severe disease. For the said purpose the reaction-diffusion HIV CD4+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{+}$$\\end{document} T cell model with drug therapy under the stochastic environment is considered. The underlying model is numerically investigated with two time-efficient schemes and the effects of various parameters used in the model are analyzed and explained in a real-life scenario. Additionally, the obtained results will help the decision-makers to avoid such diseases. The random version of the HIV model is numerically investigated under the influence of time noise in Ito^\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\hat{o}}$$\\end{document} sense. The proposed stochastic backward Euler (SBE) scheme and proposed stochastic Implicit finite difference (SIFD) scheme are developed for the computational study of the underlying model. The consistency of the schemes is proven in the mean square sense and the given system of equations is compatible with both schemes. The stability analysis proves that both schemes and schemes are unconditionally stable. The given system of equations has two equilibria, one is disease-free equilibrium (DFE) and the other is endemic equilibrium. The simulations are drawn for the different values of the parameters. The proposed SBE scheme showed the convergent behavior towards the equilibria for the given values of the parameters but also showed negative behavior that is not biological. The proposed SIFD scheme showed better results as compared with the stochastic SBE scheme. This scheme has convergent and positive behavior towards the equilibria points for the given values of the parameters. The effect of various parameters is also analyzed. Simulations are drawn to evaluate the efficacy of the schemes.

Histoplasmosis associated hemophagocytosis- a rare cause of pancytopenia in an immunocompetent patient

Pancytopenia as a result of hemophagocytosis in a middle-aged man presenting with high-grade fever of unknown etiology could be a rare consequence of Histoplasmosis infection. In the past, many cases of patients with human immunodeficiency virus infection contracting histoplasmosis-induced hemophagocytosis have been well documented, however, little data has been entered in the setting of HIV non-reactive status. Interestingly, we report a case of histoplasmosis in an immunocompetent male with the presence of yeast forms of H. capsulatum in the bone marrow smears. The patient was subsequently placed on Amphotericin B and corticosteroids but lost to the infectious disease. Cases like this, highlight the importance of taking into account the early decision for bone marrow sampling with careful attention to microscopic details as incidental pathologies may be elicited which could have significant effects on patient’s prognosis.

Severe Combined Kidney Injury in an Hiv-Infected Patient Receiving Antiretroviral Therapy (Clinical Observation)

Kidney injury in patients infected with the human immunodeficiency virus (HIV) has a diverse spectrum. Some antiretroviral therapy (ART) drugs have nephrotoxic effects. We present a clinical case of severe combined kidney injury — chronic kidney disease (CKD) and acute kidney disease (AKD) — in a patient with HIV infection. She was on long-term treatment with a fixed-dose combination of rilpivirine, tenofovir, and emtricitabine and had normal pre-treatment renal function (estimated glomerular filtration rate 69 mL/min/1.73m2 ). There was gradual increase in blood creatinine, but the patient did not visit a nephrologist and the ART was not changed. The patient was admitted to the nephrology department two years later because she had arterial hypertension and hyperazotemia (blood creatinine 718 μmol/l). Diagnosis: chronic tubulointerstitial nephritis, CKD G5 taking into account the gradual increase in blood creatinine during long-term ART. The patient was treated with peritoneal dialysis. There was persistent decrease and stabilization of blood creatinine (210-190 μmol/l was) which indicated in AKD. The presented observation demonstrates that ART in an HIVinfected patient can lead to the development of severe combined chronic and acute kidney injury. HIV-infected patients receiving ART require regular monitoring of renal function and follow-up by a nephrologist.

Double-Negative T-Cells during Acute Human Immunodeficiency Virus and Simian Immunodeficiency Virus Infections and Following Early Antiretroviral Therapy Initiation.

HIV infection significantly affects the frequencies and functions of immunoregulatory CD3+CD4-CD8- double-negative (DN) T-cells, while the effect of early antiretroviral therapy (ART) initiation on these cells remains understudied. DN T-cell subsets were analyzed prospectively in 10 HIV+ individuals during acute infection and following early ART initiation compared to 20 HIV-uninfected controls. In this study, 21 Rhesus macaques (RMs) were SIV-infected, of which 13 were assessed during acute infection and 8 following ART initiation four days post-infection. DN T-cells and FoxP3+ DN Treg frequencies increased during acute HIV infection, which was not restored by ART. The expression of activation (HLA-DR/CD38), immune checkpoints (PD-1/CTLA-4), and senescence (CD28-CD57+) markers by DN T-cells and DN Tregs increased during acute infection and was not normalized by ART. In SIV-infected RMs, DN T-cells remained unchanged despite infection or ART, whereas DN Treg frequencies increased during acute SIV infection and were not restored by ART. Finally, frequencies of CD39+ DN Tregs increased during acute HIV and SIV infections and remained elevated despite ART. Altogether, acute HIV/SIV infections significantly changed DN T-cell and DN Treg frequencies and altered their immune phenotype, while these changes were not fully normalized by early ART, suggesting persistent HIV/SIV-induced immune dysregulation despite early ART initiation.

Synthesis of Novel Indolyl Aryl Sulfone-clubbed Hydrazone Derivatives as Potential HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: Molecular Modeling and QSAR Studies.

Non-Nucleoside Reverse Transcriptases Inhibitors (NNRTIs) are among the most extensively studied enzymes for understanding the biology of Human Immunodeficiency Viruses (HIV) and designing inhibitors for managing HIV infections. Indolyl aryl sulfones (IASs), an underexplored class of potent NNRTIs, require further exploration for the development of newer drugs for HIV. In this context, we synthesized a series of novels by Indolyl Aryl Sulfones with a hydrazone moiety at the carboxylate site of the indole nucleus. A 2D-QSAR model was developed to predict Reverse Transcriptase inhibitory activity against wild-type RT (WT-RT) enzyme. The model was successfully applied to predict the HIV-1 inhibitory activity of known Indolyl Aryl Sulfones. Considering the reliability, robustness, and reproducibility of the 2D-QSAR model, we made an in-silico prediction of the RT inhibition for our synthesized compounds (1-14). Molecular docking and dynamics simulations established our synthesized Indolyl Aryl Sulfones, particularly compounds 23, 24, and 28, as effective NNRTIs by stabilizing HIV reverse transcriptase's structure. Binding energy calculations revealed compound 28 as the strongest inhibitor (-43.21 ± 0.09 kcal/mol), followed by 23 (-40.94 ± 0.10 kcal/mol) and 24 (-39.18±0.08 kcal/mol), emphasizing their binding affinity towards HIV reverse transcriptase. In summary, the synthesized Indolyl Aryl Sulfones, particularly compounds 23, 24, and 28, demonstrate significant potential as Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) against HIV. These results highlight the promising role of these compounds in developing novel NNRTIs for managing HIV infections.

From Gut to Blood: Redistribution of Zonulin in People Living with HIV.

Gastrointestinal mucosal damage due to human immunodeficiency virus (HIV) infection leads to microbial translocation and immune activation, contributing to the development of non-infectious comorbidities (NICM) in people living with HIV (PLWH). Additionally, persistent proviral HIV-1 in the gut-associated lymphatic tissue (GALT) can trigger immunological changes in the epithelial environment, impacting the mucosal barrier. However, the role of zonulin, a modulator of epithelial tight junctions in GALT during HIV infection, remains poorly understood. We measured zonulin in serum and intestinal tissue sections from five treatment-naive (HIV+NAIVE) and 10 cART-treated (HIV+cART) HIV+ individuals, along with 11 controls (CTRL). We compared zonulin levels with clinical characteristics, inflammatory markers (IFN-α, CXCR3, and PD-1), and the viral reservoir in peripheral blood (PB) and terminal ileum (TI). Upon HIV infection, TI was found to harbor more HIV DNA than PB. Circulating zonulin levels were highest in HIV+NAIVE compared to HIV+cART or CTRL. Surprisingly, in the gut tissue sections, zonulin levels were higher in CTRL than in HIV+ individuals. Elevated circulating zonulin levels were found to be correlated with CD4+T-cell depletion in PB and TI, and with intestinal IFN-α. The findings of this study indicate a shift in zonulin levels from the gut to the bloodstream in response to HIV infection. Furthermore, elevated systemic zonulin levels are associated with the depletion of intestinal CD4+ T cells and increased gut inflammation, suggesting a potential link between systemic zonulin and intestinal damage. Gaining insight into the regulation of gut tight junctions during HIV infection could offer valuable understanding for preventing NICM in PLWH.