Epidemiological risk factors associated with primary infection by Epstein-Barr virus in HIV-1-positive subjects in the Brazilian Amazon region

Health Surveillance Department of the Brazilian Ministry of Health and Conselho Nacional de Desenvolvimento Científco e Tecnológico–CNPQ (#301869/2017-0). Coordination for the Improvement of Higher Education Personnel (CAPES) (process number: 88882.183970/2018-01).Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Departamento de Epidemiologia e Vigilância. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Departamento de Epidemiologia e Vigilância. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Retrovírus. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil / Federal University of Pará. School of Medicine. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Retrovírus. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Vírus Epstein-Barr. Ananindeua, PA, Brasil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil /Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.To identify the prevalence and risk factors for primary Epstein–Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51–15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01–2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12–2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79–1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22–3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1–10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population

Epstein–Barr Virus (EBV) Genotypes Associated with the Immunopathological Profile of People Living with HIV-1: Immunological Aspects of Primary EBV Infection

Background: The aim of the present study was to evaluate the immunological profile of adult HIV-1+ patients coinfected with primary Epstein–Barr virus (EBV) infection who were free of antiretroviral drugs and inhabitants of the Brazilian Amazon region. Materials and methods: Primary EBV infection was screened by the semiquantitative detection of IgM and IgG anti-VCA. Genotypes were determined by conventional PCR. EBV and HIV viral load (VL) were quantified by real-time PCR. Cytokine dosage and cell quantification were performed by cytometry. Results: Only HIV-1+ individuals had primary EBV infection (7.12%). The EBV-1 genotype was the most prevalent (47.37%). The VL of HIV-1 was lower in the HIV/EBV-2 group. CD4+ T lymphocytes were inversely proportional to the VL of EBV in HIV/EBV-1/2 multi-infected patients. The HIV/EBV-2 group had the lowest cytokine levels, especially IFN-γ and IL-4. Different correlations were proposed for each coinfection. The late search for specific care related to HIV infection directly affected the cytokine profile and the number of CD8+ T lymphocytes. Symptoms were associated with the increase in VL of both viruses and cytokine profile. Conclusions: Different immunological profiles were associated with EBV genotypes in primary infection, with EBV-2 being more frequent in patients with low levels of HIV viral load. With late infection monitoring and consequent delay in the initiation of HAART, clinical changes and effects on the maintenance of the immune response were observed

HLA-B13, B35 and B39 alleles are closely associated with the lack of response to ART in HIV infection: a cohort study in a population of northern Brazil

Secretaria de Vigilancia em Saúde do Ministério da Saúde (Health Surveillance Secretariat of the Ministry of Health), Conselho Nacional de Desenvolvimento Cientıfíco e Tecnológico (National Council for Scientific and Technological Development; CNPQ) (no. 301869/ 2017-0) and Fundação Amazônia de Amparo a Estudos e Pesquisa – FAPESPA (ICAAF-60/2020). Coordenação de Aperfeiçoamento de Pessoal de Nıvel Superior ́ (Brazilian Federal Agency for the Support and Evaluation of Graduate Education; CAPES) for granting a scholarship (process number: 88882.183970/2018-01).Federal University of Pará. Institute of Biological Sciences. Virology Laboratory. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, BrasilHemotherapy and Hematology Foundation of the State of Pará. Department of Immunogenetics. Belém, PA, BrazilHemotherapy and Hematology Foundation of the State of Pará. Department of Immunogenetics. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Retrovirus. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, Brasil / Federal University of Pará. School of Medicine. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Laboratory of Human and Medical Genetics. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, BrazilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Retrovirus. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de vírus Epstein-Barr. Ananindeua, PA, Brasil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, BrazilFederal University of Pará. Institute of Biological Sciences. Virology Laboratory. Belém, PA, Brazil / Federal University of Pará. Institute of Biological Sciences. Graduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, BrazilIntroduction Immune reconstitution failure after HIV treatment is a multifactorial phenomenon that may also be associated with a single polymorphism of human leukocyte antigen (HLA); however, few reports include patients from the Brazilian Amazon. Our objective was to evaluate the association of the immunogenic profile of the “classical” HLA-I and HLA-II loci with treatment nonresponse in a regional cohort monitored over 24 months since HIV diagnosis. Materials and Methods Treatment-free participants from reference centers in the state of Pará, Brazil, were enrolled. Infection screening was performed using enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4 ⁺ /CD8 ⁺ T lymphocyte quantification was performed by immunophenotyping and flow cytometry (BD Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on CD4 ⁺ T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3. Results Of the 270 patients monitored, 134 responded to treatment (CD4 ⁺ ≥ 500 cells/µL), and 136 did not respond to treatment (CD4 ⁺ < 500 cells/µL). The allele frequencies of the loci were similar to heterogeneous populations. The allelic profile of locus B was statistically associated with treatment nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic influence. The B*13 allele had the highest risk of treatment nonresponse, and carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count less than 400 cells/µL with up to 2 years of therapy. The B*13 allele was associated with a switch in treatment regimens, preferably to efavirenz (EFZ)-based regimens, and among those who switched regimens, half had a history of coinfection with tuberculosis. Conclusions The allelic variants of the B locus are more associated with non-response to therapy in people living with HIV (PLHIV) from a heterogeneous population in the Brazilian Amazon

Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α

Abstract The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID