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BACKGROUND: Evaluating the clinical performance of Elecsys HIV Duo assay for primary human immunodeficiency virus (HIV) screening and acute HIV infection detection. METHODS: This study was conducted from April 2022 to April 2023 and involved two distinct populations. For the HIV screening population, three HIV Duo results [HIV Duo, HIV antigen (Ag), and HIV antibody (Ab)] in primary screening were obtained (January 2021 to June 2021). In the diagnosed HIV population, retrospective samples from November 2016 to March 2023 were measured. RESULTS: The HIV screening population included 111,383 samples from a real-world screening program. The assay demonstrated a specificity of 99.91 % (95 % CI: 99.89 %, 99.93 %) and a PPV of 0.8516 (95 % CI: 0.8225, 0.8776). Regarding the diagnosed HIV population, 836 HIV patients were enrolled, including 14 acute HIV infectious patients with only HIV Ag + and a Western Blot (WB) confirmation rate of 0 %. The median (IQR) of the numeric cut-off index (COI) ratios of HIV Duo Ab and Ag significantly differed among the Ag + Ab-, Ag-Ab+, and Ag + Ab + subgroups. CONCLUSION: The Elecsys HIV Duo assay is suitable for primary HIV screening and can be integrated into a novel laboratory HIV testing algorithm to improve acute HIV detection in Chinese clinical practice. ABBREVIATIONS: HIV, Human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome; Ag, antigen; Ab, antibody; WB, Western Blot; COI, numeric cut-off index; CI, confidence interval; NAT, nucleic acid tests; EDC, electronic data capture systems; CDC, Chinese Centers for Disease Control and Prevention; IQR, interquartile range; PPV, positive predictive value; HCV, hepatitis C virus; HBV, hepatitis B virus; CI, confidence interval; ND, not able to define; F, female; M, male.
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BACKGROUND: Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test-and-treat setting. SETTING: BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV-1 diagnosis before baseline laboratory. METHODS: The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log10 HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test. RESULTS: 36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log10 HIV-RNA was 4.79 (± 0.87) log10 copies/mL and CD4 505 (±253) cells/mm3. The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log10 HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log10 copies/mL, p < 0.001). Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events. CONCLUSION: In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF.
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Fármacos Anti-VIH , Emtricitabina , Infecciones por VIH , Tenofovir , Carga Viral , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Femenino , Adulto , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Carga Viral/efectos de los fármacos , Emtricitabina/uso terapéutico , VIH-1/efectos de los fármacos , VIH-1/genética , Adenina/análogos & derivados , Adenina/uso terapéutico , Piperazinas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Darunavir/uso terapéutico , Alanina/uso terapéutico , Alanina/análogos & derivados , Resultado del Tratamiento , ARN Viral , Sulfonamidas/uso terapéutico , Persona de Mediana Edad , Cobicistat/uso terapéutico , Reino Unido , Combinación de Medicamentos , Amidas , PiridonasRESUMEN
Background: When individuals infected with human immunodeficiency virus (HIV) experience pulmonary infections, they often exhibit severe symptoms and face a grim prognosis. Consequently, early, rapid, and accurate pathogen diagnosis is vital for informing effective treatment strategies. This study aimed to use metagenomic next-generation sequencing (mNGS) and targeted mNGS (tNGS) to elucidate the characteristics of pulmonary infections in HIV and non-HIV individuals. Methods: This study enrolled 90 patients with pulmonary infection at the Department of Infectious Diseases of The First Hospital of Jilin University from June 2022 to May 2023, and they were divided into HIV (n=46) and non-HIV (n=44) infection groups. Their bronchoalveolar lavage fluid (BALF) was collected for mNGS analysis to evaluate the differences in pulmonary infection pathogens, and tNGS detection was performed on BALF samples from 15 HIV-infected patients. Results: A total of 37 pathogens were identified in this study, including 21 bacteria, 5 fungi, 5 viruses, 5 mycobacteria, and 1 mycoplasma. The sensitivity of mNGS was 78.9% (71/90), which is significantly higher than that of conventional methods (CTM) (39/90, P=1.5E-8). The combination of mNGS with CTM can greatly enhance the sensitivity of pathogen detection. The prevalence of Pneumocystis jirovecii (82.6% vs. 9.1%), cytomegalovirus (CMV) (58.7% vs. 0%), and Epstein-Barr virus (EBV) (17.4% vs. 2.3%) was significantly higher in the HIV infection group than in the non-HIV infection group (P<0.05). Although no statistically significant difference was observed, the detection rate of Mycobacteria was higher in HIV-infected patients (17.4%) than in the non-HIV group (6.8%). Furthermore, the tNGS results of BALF from 15 HIV-infected patients were not entirely consistent with the mNGS results., and the concordance rate of tNGS for the detection of main pathogens reached 86.7% (13/15). Conclusion: Next-generation sequencing (NGS) can accurately detect pathogens in the BALF of patients with pulmonary infection. The sensitivity of tNGS is comparable to that of mNGS. Therefore, this technique should be promoted in the clinic for better patient outcomes.
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Líquido del Lavado Bronquioalveolar , Infecciones por VIH , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Masculino , Femenino , Metagenómica/métodos , Líquido del Lavado Bronquioalveolar/microbiología , Líquido del Lavado Bronquioalveolar/virología , Persona de Mediana Edad , Adulto , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Anciano , Sensibilidad y Especificidad , Virus/genética , Virus/aislamiento & purificación , Virus/clasificación , Metagenoma , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/diagnósticoRESUMEN
Despite effective antiretroviral therapy (ART), 15-30% of people with HIV experience poor CD4+ T-cell recovery, termed immunologic non-responders (INR). This study aims to evaluate whether pre-ART plasma levels of interleukin-6 (IL-6), interferon gamma-induced protein-10 (IP-10), macrophage inflammatory protein-1-ß (MIP-1ß), and/or pentraxin-3 (PTX-3) could predict subsequent immunologic recovery. Seventy-four participants were enrolled and classified as INR and immunologic responders (IR) based on CD4+/CD8+ ratio increase over 24 months after starting ART. The results showed no significant differences in cytokine levels between INR and IR. Therefore, IL-6, IP-10, MIP-1ß, and PTX-3 were unsuitable as predictive markers of poor immune recovery.
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Biomarcadores , Proteína C-Reactiva , Quimiocina CCL4 , Quimiocina CXCL10 , Infecciones por VIH , Interleucina-6 , Componente Amiloide P Sérico , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/sangre , Componente Amiloide P Sérico/metabolismo , Masculino , Femenino , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Adulto , Quimiocina CCL4/sangre , Interleucina-6/sangre , Persona de Mediana Edad , Biomarcadores/sangre , Quimiocina CXCL10/sangre , Terapia Antirretroviral Altamente Activa , Resultado del Tratamiento , Antirretrovirales/uso terapéutico , Relación CD4-CD8 , Fármacos Anti-VIH/uso terapéuticoRESUMEN
The article discusses the historical aspect and modern ideas about the etiology and pathogenesis of progressive multifocal leukoencephalopathy in patients with HIV infection. An analysis and synthesis of literature data on the clinical presentation of this pathology was carried out. The possibilities and limitations of laboratory and instrumental diagnostic methods, including neuroimaging methods, are discussed in detail. The pathomorphological signs of the disease in HIV-positive individuals are covered.
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Infecciones por VIH , Leucoencefalopatía Multifocal Progresiva , Humanos , Leucoencefalopatía Multifocal Progresiva/diagnóstico por imagen , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Infecciones por VIH/complicaciones , Virus JC/aislamiento & purificación , Imagen por Resonancia MagnéticaRESUMEN
Cat-scratch disease (CSD), caused by Bartonella henselae (B. henselae), typically presents with regional lymphadenopathy following a cat scratch or bite. We report a case of a 50-year-old man with a complex medical history including HIV, Crohn's disease, coronary artery disease, and bipolar disorder, who presented with progressively enlarging cervical lymphadenopathy associated with fever, night sweats, and myalgias. Initial evaluation suggested a neoplastic etiology, prompting extensive laboratory investigations and imaging. However, subsequent history prompted serological testing and markedly elevated Bartonella antibody titers, leading to a clinical diagnosis of CSD. Empirical doxycycline therapy was initiated, resulting in the complete resolution of symptoms. This case underscores the importance of considering CSD in the differential diagnosis of lymphadenopathy, particularly in people living with HIV regardless of immunocompetency, and highlights the challenges of diagnosis and management in complex patients.
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Background: Patients who were infected by the Human Immunodeficiency Virus (HIV) could have weakened immunity that is complicated by opportunistic infections, especially for Mycobacterium tuberculosis (MTB). Notably, the HIV-MTB co-infection will accelerate the course of disease progress and greatly increase the mortality of patients. Since the traditional diagnostic methods are time-consuming and have low sensitivity, we aim to investigate the performance of mNGS (metagenomic Next-Generation Sequencing) and mNPS (metagenomic NanoPore Sequencing) for the rapid diagnosis of tuberculosis in HIV-infected patients. Methods: The 122 HIV-infected patients were enrolled for the retrospective analysis. All of the patients underwent traditional microbiological tests, mNGS, and (or) mNPS tests. The clinical comprehensive diagnosis was used as the reference standard to compare the diagnostic performance of culture, mNGS, and mNPS on tuberculosis. We also investigate the diagnostic value of mNGS and mNPS on mixed-infection. Furthermore, the treatment adjustment directed by mNGS and mNPS was analyzed. Results: Compared with the composite reference standard, the culture showed 42.6% clinical sensitivity and 100% specificity, and the OMT(other microbiological testing) had 38.9% sensitivity and 100% specificity. The mNGS had 58.6% clinical sensitivity and 96.8% specificity, and the mNPS had 68.0% clinical sensitivity and 100% specificity. The proportion of mixed-infection cases (88.9%) in the TB group was higher than those in the non-TB group (54.8%) and the mNGS and mNPS are more competitive on mixed-infection diagnosis compared with the traditional methods. Furthermore, there are 63 patients (69.2%) and 36 patients (63.2%) achieved effective treatment after receiving the detection of mNPS and mNGS, respectively. Conclusion: Our study indicated that mNPS and mNGS have high sensitivity and specificity for TB diagnosis compared with the traditional methods, and mNPS seems to have better diagnostic performance than mNGS. Moreover, mNGS and mNPS showed apparent advantages in detecting mixed infection. The mNPS and mNGS-directed medication adjustment have effective treatment outcomes for HIV-infected patients who have lower immunity.
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Coinfección , Infecciones por VIH , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Mycobacterium tuberculosis , Secuenciación de Nanoporos , Sensibilidad y Especificidad , Tuberculosis , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Masculino , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Femenino , Infecciones por VIH/complicaciones , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Coinfección/diagnóstico , Coinfección/microbiología , Coinfección/virología , Secuenciación de Nanoporos/métodos , Metagenómica/métodosRESUMEN
With advancements in antiretroviral therapy (ART), the average lifespan of people with human immunodeficiency virus (HIV) is increasing, as is the number of older adults with HIV. Accordingly, the number of patients with HIV who undergo surgery or require critical care for various reasons is increasing. Since the prognosis of people with HIV depends on the continuous and effective maintenance of ART, there is a need to consider effectively maintaining ART in people with HIV in these conditions. This case involved a 55-year-old patient with well-controlled HIV who received ART and presented to the emergency room with acute abdominal pain. He was diagnosed with extensive bowel infarction and panperitonitis and received critical care in the intensive care unit, including mechanical ventilation and continuous renal replacement therapy. The patient was administered enteral nutrition via a nasogastric tube. The patient subsequently underwent extensive small bowel resection and developed short bowel syndrome. The patient maintained ART during that period. A literature review related to the use of ART under these conditions is included in this study. This case was discussed at the [Exploring Difficult Cases in HIV Clinics] of the Korean Society for AIDS Conference held in 2023.
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Routinely obtaining a sexual history is a necessary first step to identify which patients have specific sexual behaviours that may put them at risk and use appropriate protective measures, especially in vulnerable populations. However, late diagnosis of HIV infection remains very high. Combination prevention strategies based on condom promotion, harm reduction programs for people who inject drugs plus PrEP and HIV PEP are the best options to prevent new infections. Screening for STIs (including hepatotropic viruses) and early diagnosis and treatment are essential for the person since it improves the prognosis and complications and also for the community because it breaks the chain of transmission. People living with HIV who have an undetectable viral load do not transmit the virus sexually (undetectable=untransmittable).
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BACKGROUND: Elevated susceptibility to acute myocardial infarction and various cardiovascular diseases has been observed in individuals infected with the human immunodeficiency virus compared with the uninfected population, as demonstrated in numerous studies. The precise mechanism by which human immunodeficiency virus infection heightens the risk of acute myocardial infarction remains elusive. The manifestation of acute coronary syndrome in young patients with human immunodeficiency virus may deviate from the typical, displaying distinct pathophysiological and clinical characteristics. The occurrence of myocardial infarction with non-obstructive coronary arteries in young patients with human immunodeficiency virus poses diagnostic and treatment challenges. CASE PRESENTATION: We present the case of a 46-year-old African woman with no traditional atherosclerotic risk factors. She was diagnosed with human immunodeficiency virus-1 infection 2 years prior to her current admission for chest pain. Her troponin levels were elevated, suggestive of acute coronary syndrome. Although coronary angiography ruled out coronary artery stenosis, it revealed mild myocardial bridging in the left anterior descending artery. Cardiac magnetic resonance imaging confirmed myocardial infarction, indicating a myocardial infarction with non-obstructive coronary arteries with an apical thrombus in the left ventricle. Following medical treatment, the patient experienced resolution of chest pain and improvement in ST-segment elevation. CONCLUSIONS: In young female patients without traditional risk factors, human immunodeficiency virus infection is a possible etiological factor for myocardial infarction with non-obstructive coronary arteries. The likely pathophysiological pathway is superficial endothelial cell denudation as a result of chronic inflammation and immune activation.
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Angiografía Coronaria , Infecciones por VIH , Infarto del Miocardio , Humanos , Femenino , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Dolor en el Pecho/etiología , Electrocardiografía , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Cardiovascular disease is a major cause of morbidity in an aging HIV population. However, risk estimation with the most frequent equations usually classifies HIV patients as having a low or moderate risk. Several studies have described a very high prevalence of subclinical atherosclerosis in a middle-aged, non-HIV population. There is insufficient body of knowledge to understand if this is the case in people living with HIV (PLWH). We aim to calculate the proportion of patients with subclinical atherosclerosis in a single site cohort of HIV-infected subjects. METHODS: We have analyzed chronically HIV infected adults (≥ 18 years) who were on active follow-up in an HIV unit specialized in the care of cardiovascular health. The most recent clinical visit and vascular ultrasonography were used to assess the objectives of our research. Our primary objective was to describe the proportion of participants with subclinical atherosclerosis (focal protrusion into the lumen > 0.5 mm or > 50% of the surrounding IMT or a diffuse thickness > 1.5 mm) in a single site cohort of PLWH. Carotid and iliofemoral territories were evaluated. As a secondary objective we have run a multivariate analysis to determine which HIV and non-HIV factors might be related with the presence of atherosclerotic plaques. Findings We included a total of 463 participants between November 2017 to October 2019. Subjects were predominantly male (84.2%) with a mean age of 48.8 years (SD 10.7). Hypercholesterolemia (36%) was the most prevalent comorbidity followed by Hypertension (18%) and Hypertriglyceridemia (16%). Mean duration of HIV infection is 12.3 years. Overall, participants had been receiving cART for a median of 9.5 years. Subclinical atherosclerosis was found in 197 subjects (42.5%; CI 95% [38.0-47.2]). The disease was found more frequently in the femoral arteries (37.8%) than in the carotid vascular bed (18.6%). Despite some HIV factors correlated with the presence of plaques in a univariate analysis (e.g., time with HIV-1 RNA > 50 copies/mL or time from HIV diagnosis), the only two explanatory factors that remained associated with the presence of atherosclerotic plaques in the multivariate analysis were smoking (OR 5.47, 95% CI 3.36 - 8.90) and age (OR 1.13, 95%CI 1.10 - 1.16). Interpretation We have found a very high prevalence of subclinical atherosclerosis among our cohort of PLWH. Despite having analyzed several HIV factors, age and smoking have been found to be the only factors associated with the development of atherosclerotic plaques.
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Aterosclerosis , Arteria Femoral , Infecciones por VIH , Humanos , Masculino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Persona de Mediana Edad , Femenino , Aterosclerosis/epidemiología , Adulto , Factores de Riesgo , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/patología , Prevalencia , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Estudios de CohortesRESUMEN
Different host proteins target different HIV proteins and antagonize their functions, depending on the stage of the HIV life cycle and the stage of infection. Concurrently, HIV proteins also target and antagonize various different host proteins to facilitate HIV replication within host cells. The preceding quite specific area of knowledge in HIV pathogenesis, however, remains insufficiently understood. We therefore propose, in this review article, to examine and discuss the HIV proteins that counteract those host restriction proteins which results directly in increased infectivity of HIV. We elaborate on HIV proteins that antagonize host cellular proteins to promote HIV replication, and thus HIV infection. We examine the functions and mechanisms via which Nef, Vif, Vpu, Env, Vpr, and Vpx counteract host proteins such as Ser5, PSGL-1, IFITMS, A3G, tetherin, GBP5, SAMHD1, STING, HUSH, REAF, and TET2 to increase HIV infectivity. Nef antagonizes three host proteins, viz., Ser5, PSGL1, and IFITIMs, while Vpx also antagonizes three host restriction factors, viz., SAMHD1, STING, and HUSH complex; therefore, these proteins may be potential candidates for therapeutic intervention in HIV infection. Tetherin is targeted by Vpu and Env, PSGL1 is targeted by Nef and Vpu, while Ser5 is targeted by Nef and Env proteins. Finally, conclusive remarks and future perspectives are also presented.
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Infecciones por VIH , VIH-1 , Interacciones Huésped-Patógeno , Proteínas del Virus de la Inmunodeficiencia Humana , Humanos , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Infecciones por VIH/inmunología , Proteínas del Virus de la Inmunodeficiencia Humana/metabolismo , VIH-1/fisiología , Replicación Viral , Animales , Factores de Restricción AntiviralesRESUMEN
HIV is one of the most threatening health conditions with a highly increasing rate, affecting millions of people globally, and from its time of discovery until now, its potential cure cannot be explicitly defined. This challenge of having no/low effective drugs for the subjected virus has called for serious attention in the scientific world of virus disease therapeutics. Most of these drugs yields low effectiveness due to poor delivery; hence, there is a need for novel engineering methods for efficient delivery. In this study, two nanomaterilas (graphene; GP, and fullerene; C60) were modelled and investigated with sulfur (S), selenium (Se), and oxygen (O) atoms, to facilitate the delivery of zidovudine (ZVD). This investigation was computationally investigated using the density functional theory (DFT), calculated at B3LYP functional and Gd3bj/Def2svp level of theory. Results from the frontier molecular orbital (FMO), revealed that the GP/C60_S_ZVD complex calculated the least energy gap of 0.668 eV, thus suggesting a favourable interactions. The study of adsorption energy revealed chemisorption among all the interacting complexes wherein GP/C60_S_ZVD complex (-1.59949 eV) was highlighted as the most interacting system, thereby proving its potential for the delivery of ZVD. The outcome of this research urges that a combination of GP and C60 modified with chalcogen particularly, O, S, and Se can aid in facilitating the delivery of zidovudine.
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Reactive oxygen species (ROS) are widely regarded as signaling molecules and play essential roles in various cellular processes, but when present in excess, they can lead to oxidative stress (OS). Growing evidence suggests that the OS plays a critical role in the pathogenesis of HIV infection and is associated with several comorbidities in HIV-infected individuals. ROS, generated both naturally during mitochondrial oxidative metabolism and as a response to various cellular processes, can trigger host antiviral responses but can also promote viral replication. While the multifaceted roles of ROS in HIV pathophysiology clearly need more investigation, this review paper unravels the mechanisms of OS generation in the context of HIV infections, offering insights into HIV viral protein-mediated and antiretroviral therapy-generated OS. Though the viral protein Tat is significantly attributed to the endogenous cellular increase in ROS post HIV infection, this paper sums up the contribution of other viral proteins in HIV-mediated elicitation of ROS. Given the investigations recognizing the significant role of ROS in the onset and progression of diverse pathologies, the paper also explores the critical function of ROS in the mediation of an of array of pathologies associated with HIV infection and retroviral therapy. HIV patients are observed with disruption to the antioxidant defense system, the antioxidant therapy is gaining focus as a potential therapeutic intervention and is well discussed. While ROS play a significant role in the HIV scenario, further exploratory studies are imperative to identifying alternative therapeutic strategies that could mitigate the toxicities and pathologies associated with ART-induced OS.
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AIM: The COVID-19 pandemic posed unprecedented challenges to global healthcare, particularly affecting respiratory systems and impacting individuals with pre-existing conditions, including those with HIV. METHOD: HIV's impact on clinical outcomes was assessed in four Statistical Population, synchronized with control groups. The study also explored the influence of SARS-CoV-2 and COVID-19 treatments. Ultimately, a comparison was drawn between patients with and without HIV. RESULTS: In the first Statistical Population of COVID-19 patients with HIV, predominantly African-American men with risk factors such as obesity, hypertension, and diabetes were present. Diagnostic results showed no significant differences between the two groups. In the second Statistical Population, half of the patients were asymptomatic, with diagnoses mostly based on clinical symptoms; 6 individuals developed severe respiratory illness. In the third Statistical Population, 81â¯% of patients were treated at home, and all hospitalized patients had CD4+ lymphocyte counts above 350 cells/mm³. Most patients improved, with fatalities attributed to comorbid conditions. In the fourth Statistical Population, HIV patients were less likely to benefit from antimicrobial drugs, and mortality was higher, though synchronized analysis did not reveal significant differences. CONCLUSION: HIV patients are more susceptible to COVID-19, but the direct impact is less significant than other factors. Additional factors contribute to increased risk, while early improvement, accurate diagnosis, and intensive care reduce fatalities.
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COVID-19 , Infecciones por VIH , Humanos , COVID-19/epidemiología , COVID-19/mortalidad , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Masculino , Factores de Riesgo , Comorbilidad , Femenino , SARS-CoV-2 , Persona de Mediana Edad , AdultoRESUMEN
Background: The relationship between human immunodeficiency virus (HIV) infection and pulmonary arterial hypertension (PAH) has garnered significant scrutiny. Individuals with HIV infection have a higher risk of developing PAH. However, the specific mechanism of HIV-associated PAH remains unclear. Our study aims at investigating the shared biomarkers in HIV infection and PAH and predicting the potential therapeutic target for HIV-associated PAH. Methods: Data for HIV infection and PAH were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis was performed to detect shared genes in HIV infection and PAH. Enrichment analysis was conducted to identify the function of common DEGs. Protein-protein interaction (PPI) analysis was used to detect key genes. These crucial genes were subsequently verified by RT-qPCR. Finally, candidate drugs were identified by using the Drug Signatures Database (DSigDB). Results: Nineteen common DEGs were identified in HIV infection and PAH. Enrichment analysis exhibited that the functions of these genes were mainly enriched in inflammatory responses, mainly including cellular immunity and interaction between viral proteins and cytokines. By constructing PPI networks, we identified the key gene CC-type chemokine ligand 5 (CCL5), and we verified that CCL5 was highly expressed in hypoxia induced human pulmonary artery endothelial cells (hPAECs) and human pulmonary artery smooth muscle cells (hPASMCs). In addition, we predicted 10 potential drugs targeting CCL5 by Autodock Vina. Conclusion: This study revealed that CCL5 might be a common biomarker of HIV infection and PAH and provided a new therapeutic target for HIV-associated PAH. However, further clinical validation is still indispensable.
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Assessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population-based cancer registry data were used to identify cancer cases in both PLHIV and HIV-negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2-36.6), non-Hodgkin lymphoma (NHL) (1.6, 1.3-2.0), Hodgkin lymphoma (HL) (1.6, 1.1-2.4), cervical (2.3, 2.0-2.7), vulvar (4.0, 2.5-6.5), penile (3.0, 2.0-4.5), and eye cancers (2.2, 1.6-3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0-9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2-4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections.
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BACKGROUND: Despite successful antiretroviral therapy (ART), frequencies and immunological functions of memory CCR6+ Th17-polarised CD4+ T-cells are not fully restored in people with HIV (PWH). Moreover, long-lived Th17 cells contribute to HIV persistence under ART. However, the molecular mechanisms underlying these observations remain understudied. METHODS: mRNA-sequencing was performed using Illumina technology on freshly FACS-sorted memory CCR6+CD4+ T-cells from successfully ART-treated (ST), elite controllers (EC), and uninfected donors (HD). Gene expression validation was performed by RT-PCR, flow cytometry, and in vitro functional assays. FINDINGS: Decreased Th17 cell frequencies in STs and ECs versus HDs coincided with reduced Th17-lineage cytokine production in vitro. Accordingly, the RORγt/RORC2 repressor NR1D1 was upregulated, while the RORγt/RORC2 inducer Semaphorin 4D was decreased in memory CCR6+ T-cells of STs and ECs versus HDs. The presence of HIV-DNA in memory CCR6+ T-cells of ST and EC corresponded with the downregulation of HIV restriction factors (SERINC3, KLF3, and RNF125) and HIV inhibitors (tetraspanins), along with increased expression of the HIV-dependency factor MRE11, indicative of higher susceptibility/permissiveness to HIV-1 infection. Furthermore, markers of DNA damage/modification were elevated in memory CCR6+ T-cells of STs and ECs versus HDs, in line with their increased activation (CD38/HLA-DR), senescence/exhaustion phenotype (CTLA-4/PD-1/CD57) and their decreased expression of proliferation marker Ki-67. INTERPRETATION: These results reveal new molecular mechanisms of Th17 cell deficit in ST and EC PWH despite a successful control of HIV-1 replication. This knowledge points to potential therapeutic interventions to limit HIV-1 infection and restore frequencies, effector functions, and senescence/exhaustion in Th17 cells. FUNDING: This study was funded by the Canadian Institutes of Health Research (CIHR, operating grant MOP 142294, and the Canadian HIV Cure Enterprise [CanCURE 2.0] Team Grant HB2 164064), and in part, by the Réseau SIDA et maladies infectieuses du Fonds de recherche du Québec-Santé (FRQ-S).
Asunto(s)
Infecciones por VIH , VIH-1 , Memoria Inmunológica , Receptores CCR6 , Células Th17 , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Receptores CCR6/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , VIH-1/efectos de los fármacos , Masculino , Adulto , Femenino , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Persona de Mediana Edad , Terapia Antirretroviral Altamente Activa , Citocinas/metabolismo , Biomarcadores , Carga Viral , Perfilación de la Expresión GénicaRESUMEN
OBJECTIVE: To assess by [18F]FDG PET/MR the biomarkers of HIV-induced inflammation at baseline and 1â¯year post-antiretroviral therapy (ART). METHODS: Prospective study, 14 patients, newly diagnosed HIV-positive, asymptomatic. [18F]FDG PET/MRI (PET/MR-3.0T, Signa.GE) whole body and heart was performed, baseline and 1â¯year post-ART. Qualitative vascular assessment (hepatic reference). Quantitative assessment (SUVmax) of the whole body. T1 and T2 value estimation in 16 myocardial segments. RESULTS: Baseline CMR showed in 3 (21.4%) a decreased LVEF, normalising post-TAR. Fibrosis was ruled out (T1), with no signs of myocardial oedema (T2) at baseline or post-TAR. Four (28.6%) showed baseline vascular [18F]FDG uptake, two in ascending thoracic aorta and two in ascending and descending thoracic aorta, normalising post-TAR. All (100%) showed basal lymph-nodes activity; supra (n:14) and infradiaphragmatic (n:13), laterocervical (n:14) and inguinal (n:13), with variable number of territories (9 patients >6;64.3%). Post-ART, 7 patients (50%) showed resolution and the other 7 reduction in extension (0 patients >5): 7 supra (100%) and 2 infradiaphragmatic (28.6%), 5 in the axilla and 2 in the groin. All (100%) had persistent basal adenoid uptake post-ART, 9 (64.3%) splenic all resolved post-ART and 7 (50.5%) gastric, persistent 3 post-ART. CONCLUSIONS: Cardiovascular biomarkers by [18F]FDG PET/MR have shown baseline 28.6% of patients with large vessel activity and 21.4% with low LVEF, normalising post-ART. Inflammatory/immune biomarkers showed baseline activity in 100% of lymph-nodes, 100% adenoids, 64.3% splenic and 50.5% gastric. Post-TAR the reduction was 50% lymph-nodes, 0% adenoid, 100% splenic and 57.1% gastric.