Chronic Human Immunodeficiency Virus Research Articles

Human Immunodeficiency Virus-Induced Interferon-Stimulated Gene Expression Is Associated With Monocyte Activation and Predicts Viral Load.

Chronic immune activation is one of the hallmarks of human immunodeficiency virus (HIV) pathogenesis. Persistent upregulation of interferons (IFNs) and interferon-stimulated genes (ISGs) has previously been associated with chronic immune activation and HIV progression. Here a longitudinal analysis of the IFN and ISG response during HIV infection was performed to gain insights into the ongoing immune activation during HIV infection. IFN and ISG levels were determined using quantitative polymerase chain reaction in peripheral blood mononuclear cells of people with HIV at pre-seroconversion, during acute and chronic HIV infection, and during suppressive antiretroviral therapy (ART). HIV infection induced the expression of a set of 4 ISGs-RSAD2, ISG15, IFI44L, and IFI27-which remained upregulated during chronic infection. This set of ISGs showed no clear correlations with T-cell activation as determined by co-expression of CD38 and HLA-DR. However, a strong correlation with monocyte activation marker soluble CD163 in serum was found. Furthermore, the expression of this ISG cluster was predictive of viral load before ART initiation and, on ART, expression levels normalized to pre-seroconversion levels. The results presented here suggests that ISG expression is linked to monocyte activation, possibly driven by viral replication.

#610 Alterations in frequency and function exhausted memory B cells in lupus nephritis and systemic lupus erythematosus

Abstract Background and Aims Various B cell abnormalities have been implicated in the pathogenesis of LN, and our previous studies have demonstrated that memory B cells assume pathogenic relevance in disease relapse. Memory B cell exhaustion is a B lymphocyte aberration initially reported in chronic human immunodeficiency virus (HIV) infection, and was later also observed in chronic graft versus host disease (cGVHD) and autoimmune disorders. The pathogenic roles of exhausted memory B cells in LN and disease relapse remains unclear. We will validate the significance role of exhausted B cell in the pathogenesis of LN. Method Classical memory (CD19 + CD21 + CD27+) and exhausted B cells (CD19 + CD21 – CD27–) were measured in LN patients with multiple relapses (MR) (n=15) or no relapse (NR) (n=15) during disease remission. B cell-related cytokines, homing and inhibitory receptors, proliferation and calcium mobilization in classical and exhausted memory B cells were also assessed. Using single-cell RNA sequencing data from NIH and GEO, we also performed bioinformatics analysis to identify genes and pathways relevant to memory and exhausted B cells in SLE, LN and healthy controls. Results The MR group exhibited higher proportion of circulating exhausted memory B cells compared to NR. Blood levels of IL-6, BAFF and IL-21 in MR patients were higher than the NR group. The MR had higher blood levels of Siglec-6, CXCR3 and CD62L than the NR group. Expression of inhibitory receptors CD22, CD85j, CD183 and FCRL4 in exhausted B cells were increased in the MR group compared to the NR group. Exhausted B cells from MR patients also showed decreased proliferation compared to NR patients and impaired calcium mobilization in response to B-cell receptor triggering. STAT1, XAF1, MX1, IFI44L, EPSTI1, LCP1, OAS1, NEAT1, IFI16, IFI44 in exhausted B cells and XAF1, MX1, IFI44L in memory B cells play a pathogenic role in LN patients (Figs. 1 and 2). SLE patients also show increased proportion of exhausted B cells compared to healthy control and the expression of STAT1, XAF1, MX1, IFI44L correlate positively with the proportion of exhausted B cells. Conclusion Our results suggested that altered numbers and function of exhausted B cells may have pathogenic significance in SLE and LN.

A bibliometric analysis of HIV nursing research between 1999 and 2022.

Human immunodeficiency virus (HIV) nursing has become more prominent with the increase in chronic HIV infections. This study examined articles related to HIV nursing to determine how the profession has developed and its future direction. A bibliometric analysis was conducted. HIV nursing-related articles published in the Web of Science core collection between 1999 and 2022 were searched. VOSviewer was used to identify the contributions of countries, institutions and authors in HIV-related care. Collaborative maps, hot topics and keywords trends were analysed using VOSviewer and CiteSpace. A total of 1513 publications were extracted. An increase in articles published between 1999 and 2012 was observed. After 2012, the increase in the number of publications was relatively stable. Since 2016, a downward trend in the number of publications has occurred. The USA, South Africa and the UK were the leading contributors to publications related to HIV nursing. The focus of the HIV nursing research has gradually shifted from "HIV infection", "risk factors", and "transmission routes" to "social support", "depression", and "public health". The result shows that increased collaboration among countries/regions can improve the development of HIV nursing and effectively reduce the global HIV infection rate. The mental health of patients has become a research centre in the field of HIV nursing. This study provides direction in clinical practice and future research areas in this field.

Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors.

Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.

Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection.

Chronic Human Immunodeficiency Virus (HIV) infection remains a significant challenge to global public health. Despite advances in antiretroviral therapy (ART), which has transformed HIV infection from a fatal disease into a manageable chronic condition, a definitive cure remains elusive. One of the key features of HIV infection is chronic immune activation and inflammation, which are strongly associated with, and predictive of, HIV disease progression, even in patients successfully treated with suppressive ART. Chronic inflammation is characterized by persistent inflammation, immune cell metabolic dysregulation, and cellular exhaustion and dysfunction. This review aims to summarize current knowledge of the interplay between chronic inflammation, immune metabolism, and T cell dysfunction in HIV infection, and also discusses the use of humanized mice models to study HIV immune pathogenesis and develop novel therapeutic strategies.

Safety and Virologic Impact of Haploidentical NK Cells Plus Interleukin 2 or N-803 in HIV Infection.

Natural killer (NK) cells are dysfunctional in chronic human immunodeficiency virus (HIV) infection as they are not able to clear virus. We hypothesized that an infusion of NK cells, supported by interleukin 2 (IL-2) or IL-15, could decrease virus-producing cells in the lymphatic tissues. We conducted a phase 1 pilot study in 6 persons with HIV (PWH), where a single infusion of haploidentical related donor NK cells was given plus either IL-2 or N-803 (an IL-15 superagonist). The approach was well tolerated with no unexpected adverse events. We did not pretreat recipients with cyclophosphamide or fludarabine to "make immunologic space," reasoning that PWH on stable antiretroviral treatment remain T-cell depleted in lymphatic tissues. We found donor cells remained detectable in blood for up to 8 days (similar to what is seen in cancer pretreatment with lymphodepleting chemotherapy) and in the lymph nodes and rectum up to 28 days. There was a moderate decrease in the frequency of viral RNA-positive cells in lymph nodes. There was a moderate decrease in HIV-producing cells in lymph nodes. Further studies are warranted to determine the impact of healthy NK cells on HIV reservoirs and if restoring NK-cell function could be part of an HIV cure strategy. Clinical Trials Registration. NCT03346499 and NCT03899480.

Attitudes and perceptions about COVID‐19 vaccination in the population with chronic HIV infection: A systematic review

AbstractBackground and AimsThe coronavirus disease 2019 (COVID‐19)‐infected population has been increasing during the last 3 years worldwide. Moreover, simultaneously, COVID‐19 vaccine clinical trials were launched. By the end of 2020, the Food and Drug Administration had authorized the emergency use of two messenger RNA vaccines against COVID‐19. These fast‐track vaccine approvals have produced controversy about their safety and efficacy. The purpose of this research was to discover attitudes and perceptions regarding vaccination against COVID‐19 disease among vulnerable groups such as human immunodeficiency virus (HIV)‐infected patients.MethodsBetween June 2, 2021 and March 4, 2022, we conducted a cross‐sectional study through a survey of high‐risk patients with severe COVID‐19, such as HIV‐infected patients in the Infectious Diseases Unit (Hospital Clínico Universitario San Juan, Alicante). For the data collection strategy, a nonprobabilistic snowball sampling was adopted. A structured, anonymous, self‐administered questionnaire was developed in which questions and statements were designed to evaluate their attitudes and perceptions about COVID‐19 vaccination. Descriptive and bivariate analyses were performed for the obtained data.ResultsForty‐eight participants were recruited with a mean age of 51.5 ± 11.9 years. Thirty‐nine of them (81.3%) were male. The acceptance rate of COVID‐19 vaccination was extremely high (95.7%). Bivariate analysis showed older patients significantly received a higher proportion of vaccine doses at the time of the survey (p = 0.047). Older patients were more aware of the vaccine safety controversy (61.1%) compared to younger patients (p = 0.054). There were no other significant differences between groups among questions regarding safety, efficacy, or attitudes about COVID‐19 vaccination.ConclusionAn extremely high degree of acceptance for COVID‐19 vaccination was reported. Older patients were more aware of the vaccine safety controversy. Medical staff is the most trustworthy source of information, far above all other sources. Social networks and opinion leaders have not been shown to significantly influence our population.

CD57 T cells associated with immunosenescence in adults living with HIV or AIDS.

Despite the advancement of human immunodeficiency virus (HIV)-related discoveries, new HIV infections still persist. With the advent of antiretroviral therapy, prognosis has migrated from acute to chronic HIV infection and inflammation, with the possibility of increased immune aging. We aimed to assess such immunosenescence by analysing CD27 and CD57 expression on the surface of T cells. This cross-sectional study was conducted between 2017 and 2018 on people living with HIV/AIDS (PLWHA) who attended an outpatient clinic of the Infectious Diseases Service of a university hospital and a geriatric reference service in Brazil. A standardized interview was conducted, and venous peripheral blood was collected for flow cytometry analysis. To assess immunosenescence, we compared CD27 and CD57 expression on the surface of T cells between adult and elderly individuals without HIV and adult PLWHA. All results for cells in terminal senescent stages in adult PLWHA more closely resembled those of elderly than adult participants without HIV (p > 0.05). The presence of CD27+ cells did not differ statistically among the three study groups when comparing immunological responders (IR) and immunological non-responders (INR); for the entire CD4+ T-cell population (including CD4 + CD8+ and CD4 + CD8- cells), the median count (25-75th) was higher in the INR (79.6%) than the IR (68.0%) group. HIV-infected individuals possessed a higher number of T lymphocytes with a molecular phenotype associated with immunosenescence, a lower proportion of T cells in the early stages of senescence (median 25-75th: 27.0%), and a higher proportion of T cells in the intermediate and final stages of senescence (median 25-75th: 16.1%) than adults without HIV (median 25-75th: 42.0% and 18.4%, respectively). Considering the higher number of senescent T lymphocytes, we observed in our PLWHA population-especially in the INR group (CD8CD57+ cells: 39.3% INR vs. 23.4% IR; CD4CD57+ cells: 44.0% INR vs. 27.7% IR)-may indicate a similar mortality risk phenotype from immune-preventable diseases.

Integrated analysis of gut and oral microbiome in men who have sex with men with HIV Infection.

Human immunodeficiency virus (HIV) infection leads to severe deficiency in host immunity by depletion of CD4+ T-cells, resulting in an imbalance between the human microbiome and host immune response. Alterations in both gut and oral microbiomes have been observed in people living with HIV (PLWH). However, the impact of an altered gut and oral microbiome on HIV disease progression and the relationship between them in PLWH have not been explored. In this longitudinal study, we enrolled acute HIV-infected men who have sex with men (MSM) (n = 15), chronic HIV-infected MSM (n = 15), and HIV-uninfected MSM controls (n = 15). We collected anal and throat swab samples at recruitment (W0) from all participants and at 12 wk after antiretroviral therapy (ART) (W12) from the patients and performed 16S rRNA gene sequencing of genomic DNAs extracted from these swabs. In HIV-infected individuals with CD4 T-cell counts < 350 cells/µL, the increase in abundance of Streptococcus in the oral microbiome was inversely correlated with that of Streptococcus in the gut microbiome (r = -0.490, P = 0.039). In addition, the lower CD4+ T-cell counts (<200 cells/µL) were associated with the higher abundance of Escherichia-Shigella and the lower abundance of Methylobacterium-Methylorubrum of the gut microbiome in HIV-infected individuals. We demonstrate the alteration of gut microbiome resulting from HIV infection and ART and the relationship between the gut and oral microbiome in PLWH and controls. These findings highlight the need for a better understanding of the interactions between the oral and gut microbiome and its potential role in HIV disease progression. IMPORTANCE Our longitudinal integrated study has shown the marked alterations in the gut and oral microbiome resulting from acute and chronic HIV infection and from antiretroviral therapy. Importantly, the relationship between oral and gut microbiomes in people living with acute and chronic HIV infection and "healthy" controls has also been explored. These findings might contribute to a better understanding of the interactions between the oral and gut microbiomes and its potential role in HIV disease progression.

KLRG1 expression on natural killer cells is associated with HIV persistence, and its targeting promotes the reduction of the viral reservoir

Human immunodeficiency virus (HIV) infection induces immunological dysfunction, which limits the elimination of HIV-infected cells during treated infection. Identifying and targeting dysfunctional immune cells might help accelerate the purging of the persistent viral reservoir. Here, we show that chronic HIV infection increases natural killer (NK) cell populations expressing the negative immune regulator KLRG1, both in peripheral blood and lymph nodes. Antiretroviral treatment (ART) does not reestablish these functionally impaired NK populations, and the expression of KLRG1 correlates with active HIV transcription. Targeting KLRG1 with specific antibodies significantly restores the capacity of NK cells to kill HIV-infected cells, reactivates latent HIV present in CD4+ Tcells co-expressing KLRG1, and reduces the intact HIV genomes in samples from ART-treated individuals. Our data support the potential use of immunotherapy against the KLRG1 receptor to impact the viral reservoir during HIV persistence.

MicroRNA signature from extracellular vesicles of HCV/HIV co-infected individuals differs from HCV mono-infected

Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression. We aimed to characterize the plasma-derived EVs miRNA signature of chronic HCV infected and HIV coinfected patients to unravel the molecular mechanisms of coinfection. EVs were purified and characterized from 50 plasma samples (21 HCV mono- and 29 HCV/HIV co-infected). EV-derived small RNAs were isolated and analyzed by massive sequencing. Known and de novo miRNAs were identified with miRDeep2. Significant differentially expressed (SDE) miRNA identification was performed with generalized linear models and their putative dysregulated biological pathways were evaluated. Study groups were similar for most clinical and epidemiological characteristics. No differences were observed in EVs size or concentration between groups. Therefore, HCV/HIV co-infection condition did not affect the concentration or size of EVs but produced a disturbance in plasma-derived EVs miRNA cargo. Thus, a total of 149 miRNAs were identified (143 known and 6 de novo) leading to 37 SDE miRNAs of which 15 were upregulated and 22 downregulated in HCV/HIV co-infected patients. SDE miRNAs regulate genes involved in inflammation, fibrosis, and cancer, modulating different biological pathways related to HCV and HIV pathogenesis. These findings may help to develop new generation biomarkers and treatment strategies, in addition to elucidate the mechanisms underlying virus–host interaction.Key messagesHCV and HCV/HIV displayed similar plasma-EV size and concentration.EVs- derived miRNA profile was characterized by NGS.37 SDE miRNAs between HCV and HCV/HIV were observed.SDE miRNAs regulate genes involved in inflammation, fibrosis and cancer.

Trends from the Last Decade with Nontuberculous Mycobacteria Lung Disease (NTM-LD): Clinicians' Perspectives in Regional Center of Pulmonology in Bydgoszcz, Poland.

Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. To evaluate the clinical significance of NTM isolated from specimens and assess the frequency and clinical relevance of isolation of NTM in the Regional Center of Pulmonology in Bydgoszcz, hospital of Northern Poland. Clinical, radiological, and microbiological data were collected from all patients from whom NTM was isolated between 2013 and 2022. Data were reviewed retrospectively. Diagnostic criteria for NTM-LD published by the American Thoracic Society (ATS) were used to determine clinical relevance. The study comprised 81,985 clinical specimens submitted for mycobacterial culture in the Department of Microbiology at the Regional Center of Pulmonology in Bydgoszcz between 2013 and 2022. Clinical specimens were processed according to the standard procedure in mycobacteria laboratories in Poland. NTM strains were identified using analysis of mycolic acids by chromatography as well as GenoType NTM-DR, GenoType Mycobacterium AS, and GenoType Mycobacterium CM. There were 395 patients with NTM strains between 2013 and 2022. Out of them, 149 cases met the diagnostic criteria of NTM-LD and were classified as definite cases. M. kansasii (n = 77) was the most common species in the group (51.68%), followed by M. avium complex (n = 46). Patients with NTM-LD were 22-88 years old (median age was 60 years). There were 81 men and 68 women. The most common symptoms were cough, hemoptysis, and fever. Radiological X-ray images were dominated by infiltrative lesions in the upper and middle lobe of the right lung with cavities; the changes were in the upper lobe of the left lung and on both sides of the chest. They were smokers in 61%. The most common concomitant diseases were chronic obstructive pulmonary disease (COPD), diabetes mellitus, pulmonary carcinoma, and human immunodeficiency virus (HIV) infection, and other immunodeficiencies. The most common treatment was isoniazid, ethambutol, rifampicin, and ofloxacin for 18 months with a minimum of 12 months of culture negativity. NTM-LD infections are present with other pulmonary illnesses and extrapulmonary diseases and may be connected to primary immunologic deficiencies. These diseases concern patients of all ages and have various clinical manifestations. M. kansasii and MAC are the most prevalent NTM isolates among respiratory samples in Northern Poland. In addition, an increase in MAC and a decrease in M. kansasii both in cultivation and the cause of NTM-LD were reported.

Implementing integrated care clinics for HIV-infection, diabetes and hypertension in Uganda (INTE-AFRICA): process evaluation of a cluster randomised controlled trial

BackgroundSub-Saharan Africa is experiencing a dual burden of chronic human immunodeficiency virus and non-communicable diseases. A pragmatic parallel arm cluster randomised trial (INTE-AFRICA) scaled up ‘one-stop’ integrated care clinics for HIV-infection, diabetes and hypertension at selected facilities in Uganda. These clinics operated integrated health education and concurrent management of HIV, hypertension and diabetes. A process evaluation (PE) aimed to explore the experiences, attitudes and practices of a wide variety of stakeholders during implementation and to develop an understanding of the impact of broader structural and contextual factors on the process of service integration.MethodsThe PE was conducted in one integrated care clinic, and consisted of 48 in-depth interviews with stakeholders (patients, healthcare providers, policy-makers, international organisation, and clinical researchers); three focus group discussions with community leaders and members (n = 15); and 8 h of clinic-based observation. An inductive analytical approach collected and analysed the data using the Empirical Phenomenological Psychological five-step method. Bronfenbrenner’s ecological framework was subsequently used to conceptualise integrated care across multiple contextual levels (macro, meso, micro).ResultsFour main themes emerged; Implementing the integrated care model within healthcare facilities enhances detection of NCDs and comprehensive co-morbid care; Challenges of NCD drug supply chains; HIV stigma reduction over time, and Health education talks as a mechanism for change. Positive aspects of integrated care centred on the avoidance of duplication of care processes; increased capacity for screening, diagnosis and treatment of previously undiagnosed comorbid conditions; and broadening of skills of health workers to manage multiple conditions. Patients were motivated to continue receiving integrated care, despite frequent NCD drug stock-outs; and development of peer initiatives to purchase NCD drugs. Initial concerns about potential disruption of HIV care were overcome, leading to staff motivation to continue delivering integrated care.ConclusionsImplementing integrated care has the potential to sustainably reduce duplication of services, improve retention in care and treatment adherence for co/multi-morbid patients, encourage knowledge-sharing between patients and providers, and reduce HIV stigma.Trial registration numberISRCTN43896688.

Efficacy and Safety of Two-Drug Regimens That Are Approved from 2018 to 2022 for the Treatment of Human Immunodeficiency Virus (HIV) Disease and Its Opportunistic Infections.

The human immunodeficiency virus (HIV) is a type of virus that targets the body's immune cells. HIV infection can be divided into three phases: acute HIV infection, chronic HIV infection, and acquired immunodeficiency syndrome (AIDS). HIV-infected people are immunosuppressed and at risk of developing opportunistic infections such as pneumonia, tuberculosis, candidiasis, toxoplasmosis, and Salmonella infection. The two types of HIV are known as HIV-1 and HIV-2. HIV-1 is the predominant and more common cause of AIDS worldwide, with an estimated 38 million people living with HIV-1 while an estimated 1 to 2 million people live with HIV-2. No effective cures are currently available for HIV infection. Current treatments emphasise the drug's safety and tolerability, as lifelong management is needed to manage HIV infection. The goal of this review is to study the efficacy and safety of newly approved drugs from 2018 to 2022 for the treatment of HIV by the United States Food and Drug Administration (US-FDA). The drugs included Cabotegravir and Rilpivirine, Fostemsavir, Doravirine, and Ibalizumab. From the review, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) was shown to be noninferior to the continuation of the previous regimen, efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) in virologically suppressed adults with HIV-1. However, DOR/3TC/TDF had shown a preferable safety profile with lower discontinuations due to adverse events (AEs), lower neuropsychiatric AEs, and a preferable lipid profile. Ibalizumab was also safe, well tolerated, and had been proven effective against multiple drug-resistant strains of viruses.

Evaluation of serum calcitonin gene related peptide (CGRP) Level in HIV infected patients as an indicator of disease activity

Human immunodeficiency virus (HIV) infection is under global attention due to its rapid spread and high rate of morbidity and mortality. HIV gets an access into the mucosa of genital epithelium through binding to Langerhans cells. While viral load and CD4+ cell count are the main parameters to detect disease activity, new biomarkers are introduced as a potential parameter for monitoring of disease activity in HIV infected patients. Calcitonin Gene Related Peptide (CGRP) is a neuropeptide that is secreted by peripheral neurons at genital epithelia and plays an important role in limitation of HIV transmission and spread to infected CD4+ cells through its effect onto Langerhans cells. This study aimed to evaluate the serum level of CGRP in HIV infected patients and to determine whether CGRP can serve as an indicator of HIV infection activity. The study included 104 HIV patients and 24 normal controls. Patients were divided into four groups. Serum levels of CGRP were measured by ELISA and correlated to viral load and CD4+ cells count for patients in the four groups: primary HIV infection (PHI), chronic HIV infection (CHI) before combinational antiretroviral therapy (cART-naïve), chronic HIV infection after one year of cART-initiation, and chronic HIV infection after two years of cART. Serum levels of CGRP were also measured in sera of controls and compared to patients' groups. Serum levels of CGRP were significantly lower in cART naïve PHI and CHI patients in comparison with normal controls (p < 0.05), Also, serum CGRP levels were positively correlated with CD4+ cells count (p < 0.01), but negatively correlated with viral load (p>0.05). In conclusion, CGRP could be proposed as an indicator of disease activity in HIV patients.

Acquired haemophilia A in southern Switzerland from 2013 to 2019: a case series

Acquired haemophilia A is a rare disease with an annual incidence of 1.48 per million. Based on clinical observations, we suspect a higher incidence in southern Switzerland, and aimed at providing local epidemiological data, and clinical information regarding diagnosis, treatment and outcome in our region. All adult patients with acquired haemophilia A treated between 2013 and 2019 in our facility were included in the present retrospective analysis. We treated 11 patients with acquired haemophilia A between 2013 and 2019, resulting in an annual incidence of 4.5 per million (95% confidence interval [CI] 0-9.0). Median delay from first symptoms to diagnosis was 4.5 days, and the median age at diagnosis was 79 years (range 23-87). Possible causative conditions were: pregnancy (n = 1), polyarteritis nodosa (n = 1), myelodysplastic syndrome (n = 1), chronic human immunodeficiency virus (HIV) (n = 1), and HIV postexposure prophylaxis (n = 1). In five patients no underlying or associated condition was identified. Median activated partial thromboplastin time (aPTT)) at baseline was 79 seconds (65-117; ref. value <38 sec), and FVIII:C 2.15% (<1-3.75%). A FVIII:C <1% was present in 4/10 patients. Median FVIII-inhibitor titre was 10.3 BU/ml (2.4-75.0 BU/ml). All patients had bleeding symptoms, 5/10 patients had major bleedings, and 7/10 patients were treated with bypassing agents. All patients received corticosteroids; 7/10 patients received immunosuppressive combination therapy. FVIII levels of ≥50% were achieved after a median of 40 days (8-62). One patient had a severe immunosuppressive therapy-related infection. An 87-years-old woman died for reasons not related to acquired haemophilia A or immunosuppressive therapy. Acquired haemophilia A is a rare disease, but manageable despite the advanced patient age and comorbidities. Its incidence in Southern Switzerland is higher than previously suspected.

Mitoquinone Mesylate and Mitochondrial DNA in End Organs in Humanized Mouse Model of Chronic Treated Human Immunodeficiency Virus Infection.

No treatment exists for mitochondrial dysfunction, a contributor to end-organ disease in human immunodeficiency virus (HIV). The mitochondrial antioxidant mitoquinone mesylate (MitoQ) attenuates mitochondrial dysfunction in preclinical mouse models of various diseases but has not been used in HIV. We used a humanized murine model of chronic HIV infection and polymerase chain reaction to show that HIV-1-infected mice treated with antiretroviral therapy and MitoQ for 90 days had higher ratios of human and murine mitochondrial to nuclear DNA in end organs compared with HIV-1-infected mice on antiretroviral therapy. We offer translational evidence of MitoQ as treatment for mitochondrial dysfunction in HIV.

Controversies in the Design of Strategies for the Cure of HIV Infection.

The cure for chronic human immunodeficiency virus (HIV) infections has been a goal pursued since the antiretroviral therapy that improved the clinical conditions of patients became available. However, the exclusive use of these drugs is not enough to achieve a cure, since the viral load rebounds when the treatment is discontinued, leading to disease progression. There are several theories and hypotheses about the biological foundations that prevent a cure. The main obstacle appears to be the existence of a latent viral reservoir that cannot be eliminated pharmacologically. This concept is the basis of the new strategies that seek a cure, known as kick and kill. However, there are other lines of study that recognize mechanisms of persistent viral replication in patients under effective treatment, and that would modify the current lines of research on the cure of HIV. Given the importance of these concepts, in this work, we propose to review the most recent evidence on these hypotheses, covering both the evidence that is positioned in favor and against, trying to expose what are some of the challenges that remain to be resolved in this field of research.

Residual Central Nervous System Immune Activation Is Not Prevented by Antiretroviral Therapy Initiated During Early Chronic HIV Infection.

Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or ≥3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). In total, 185 people with HIV (median, 79 [interquartile range, 55-128] months on ART) were included. A significant inverse correlation was found between CD4+ T-cell count and CSF neopterin only at baseline (r = -0.28, P = .002), but not after 1 (r = -0.026, P = .8) or ≥3 (r -0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4+ T-cell strata after 1 or ≥3 (median, 6.6) years of ART. In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4+ T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.

Enhanced Identification of Hispanic Ethnicity Using Clinical Data: A Study in the Largest Integrated United States Health Care System.

Collection of accurate Hispanic ethnicity data is critical to evaluate disparities in health and health care. However, this information is often inconsistently recorded in electronic health record (EHR) data. To enhance capture of Hispanic ethnicity in the Veterans Affairs EHR and compare relative disparities in health and health care. We first developed an algorithm based on surname and country of birth. We then determined sensitivity and specificity using self-reported ethnicity from the 2012 Veterans Aging Cohort Study survey as the reference standard and compared this to the research triangle institute race variable from the Medicare administrative data. Finally, we compared demographic characteristics and age-adjusted and sex-adjusted prevalence of conditions in Hispanic patients among different identification methods in the Veterans Affairs EHR 2018-2019. Our algorithm yielded higher sensitivity than either EHR-recorded ethnicity or the research triangle institute race variable. In 2018-2019, Hispanic patients identified by the algorithm were more likely to be older, had a race other than White, and foreign born. The prevalence of conditions was similar between EHR and algorithm ethnicity. Hispanic patients had higher prevalence of diabetes, gastric cancer, chronic liver disease, hepatocellular carcinoma, and human immunodeficiency virus than non-Hispanic White patients. Our approach evidenced significant differences in burden of disease among Hispanic subgroups by nativity status and country of birth. We developed and validated an algorithm to supplement Hispanic ethnicity information using clinical data in the largest integrated US health care system. Our approach enabled clearer understanding of demographic characteristics and burden of disease in the Hispanic Veteran population.