RESUMO

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-É£, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties.

Assuntos

Coinfecção , Citocinas , Infecções por Vírus Epstein-Barr , Infecções por HIV , HIV-1 , Herpesvirus Humano 4 , Polimorfismo de Nucleotídeo Único , Humanos , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Infecções por HIV/complicações , Brasil/epidemiologia , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/complicações , Masculino , Adulto , Feminino , HIV-1/imunologia , HIV-1/genética , Citocinas/genética , Citocinas/sangue , Pessoa de Meia-Idade , Coinfecção/virologia , Coinfecção/imunologia , Coinfecção/genética , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/genética , Genótipo , Linfócitos T CD8-Positivos/imunologia , Adulto Jovem , Contagem de Linfócito CD4 , Imunogenética

RESUMO

This study aimed to analyze the prevalence, sociobehavioral factors and clinical-laboratory consequences of late presentation among people living with HIV (PLHIV) in the Brazilian Amazon region. In total, 402 HIV + individuals treated at reference units in Belém city (Pará, Brazil) between 2018 and 2019 were evaluated. Late presentation was defined as a first-collection LTCD4+ count below 350 cells/µL. Sociodemographic, behavioral and clinical data were obtained from questionnaires or medical records. Th1, Th2 and Th17 cytokine profiles were evaluated by flow cytometry. Longitudinal data on viral load, T lymphocytes, and antiretroviral therapy administration were obtained from control and logistic databases. Approximately 52.73% of the participants were late presenters and sought medical care 7-12 + months after their primary HIV diagnosis. Sociobehavioral factors associated with late presentation included illicit drug use for more than 5 years, polyamory, no alcohol consumption, homosexuality, and sexual inactiveness after HIV diagnosis. Clinically, late presentation was associated with coinfection rate; polysymptomatology; high IFN-É£, IL-6 and IL-10 levels; nonresponse to antiretroviral therapy; and virological failure- and tuberculosis coinfection-motivated changes to therapy. In summary, the prevalence of late presentation in Pará in the Brazilian Amazon region is high. Delays in seeking specialized care after a primary HIV diagnosis cause medium/long-term changes in the life expectancy and health of PLHIV.

RESUMO

Background: Epstein-Barr virus (EBV) infection involves distinct clinical and serological profiles. We evaluated the frequency of alleles of locus DRB1 of HLA class II in different serological profiles of EBV infection among HIV-1 infected patients. Methods: We recruited 19 patients with primary infection, 90 with serological transition and 467 with past infection by EBV, HIV-1 co-infection was 100% in primary infection and approximately 70% in other serological profiles. EBV viral load was quantified by real-time PCR, T lymphocyte quantification and cytokine level analysis were performed by flow cytometry, and HLA locus genotyping was performed by PCR-SSO. Results: The DRB1*09 allele was associated with primary infection (p: 0.0477), and carriers of the allele showed changes in EBV viral load (p: 0.0485), CD8(+) T lymphocyte counts (p: 0.0206), double-positive T lymphocyte counts (p: 0.0093), IL-4 levels (p: 0.0464) and TNF levels (p: 0.0161). This allele was also frequent in HIV-coinfected individuals (p: 0.0023) and was related to the log10 HIV viral load (p: 0.0176) and CD8(+) T lymphocyte count (p: 0.0285). In primary infection, the log10 HIV viral load was high (p: 0.0060) and directly proportional to the EBV viral load (p: 0.0412). The DRB1*03 allele correlated with serological transition (p: 0.0477), EBV viral load (p: 0.0015), CD4(+) T lymphocyte count (p: 0.0112), CD8(+) T lymphocyte count (p: 0.0260), double-negative T lymphocyte count (p: 0.0540), IL-4 levels (p: 0.0478) and IL-6 levels (p: 0.0175). In the serological transition group, the log10 HIV viral load was high (p: 0.0060), but it was not associated with the EBV viral load (p: 0.1214). Past infection was related to the DRB1*16 allele (p: 0.0477), with carriers displaying IgG levels (p: 0.0020), CD4(+) T lymphocyte counts (p: 0.0116) and suggestive CD8(+) T count alterations (p: 0.0602). The DRB01*16 allele was also common in HIV-1 patients with past EBV infection (p: 0.0192); however, the allele was not associated with clinical markers of HIV-1 infection. Conclusion: Our results suggest that HLA class II alleles may be associated with the modulation of the serological profiles of the immune response to Epstein-Barr virus infection in patients coinfected with HIV-1.

RESUMO

We field-assessed the accuracy, acceptability, and feasibility of the SD BIOLINE HIV/Syphilis Duo rapid diagnostic test in three groups: pregnant women, female sex workers (FSW), and men who have sex with men (MSM). Venous blood samples collected in the field were compared with the respective gold standard methods: SD BIOLINE HIV/Syphilis Duo Treponemal Test versus FTA-abs (Wama brand) treponemal laboratory test for syphilis, and SD BIOLINE HIV/Syphilis Duo Test versus the fourth generation Genscreen Ultra HIV Ag-Ag (Bio-Rad brand) laboratory test for HIV. From a total of 529 participants, 397 (75.1%) were pregnant women, 76 (14.3%) FSW and 56 (10.6%) MSM. Sensitivity and specificity parameters of HIV were 100.0% (95% CI: 82.35-100.0%) and 100.0% (95% CI: 99.28-100.0%), respectively. Sensitivity and specificity parameters found for TP antibody detection were 95.00% (95% CI: 87.69-98.62%) and 100.0% (95% CI: 98.18-100.0%), respectively. The SD BIOLINE HIV/Syphilis Duo Test showed high acceptability among participants (85.87%) and health professionals (85.51%), as well as easy usability by professionals (91.06%). The usability of the SD BIOLINE HIV/Syphilis Duo Test kit would not be a barrier to accessing rapid testing, if the product were incorporated into the list of health service supplies.

RESUMO

Introduction: 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.

Assuntos

Infecções por HIV , Alelos , Brasil , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Antígenos HLA/genética , Antígenos HLA-B/genética , Humanos

RESUMO

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.

Assuntos

Infecções por Vírus Epstein-Barr/virologia , Infecções por HIV/imunologia , HIV-1/imunologia , Herpesvirus Humano 4/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Coinfecção , Estudos Transversais , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Feminino , Genótipo , Infecções por HIV/virologia , Soropositividade para HIV , Herpesvirus Humano 4/imunologia , Humanos , Imunidade , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem

RESUMO

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.

Assuntos

Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por HIV/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Testes Sorológicos/estatística & dados numéricos , Sexualidade/estatística & dados numéricos , Fatores Socioeconômicos , Carga Viral

RESUMO

Acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) is a major global public health problem. The aim of this study is to determine the prevalence of HIV-1 infection in four municipalities of Pará State (Marabá, Parauapebas, Curionópolis, and Canaã dos Carajás), in northern, Brazil. The municipalities are located in the Carajás Complex iron mining area. The employment opportunities result in extensive migratory flow of people. A total of 4771 serum samples were obtained from 2005 to 2014 and were sent to Evandro Chagas Institute, Belém-Pará, where they were tested by enzyme-linked immunosorbent assay, with reactive samples confirmed by Western blot analysis. The samples were from individuals from 23 Brazilian states and the Federal District, mainly Maranhão (39.53%) and other municipalities of Pará (34.25%). The total positivity rate was 0.48% (23/4771). The rate was 0.47% (14/2975) in males and 0.50% (9/1796) in females. Of these, 0.33% (14/4275) were from asymptomatic individuals whose serum were collected during the serological survey, 1.81% (9/497) were from cases featuring clinical symptoms including fever/diarrhea/jaundice, which were included in febrile, diarrheal, and icteric syndromes analyzed during the study. The findings indicated the presence of HIV-1 infection in the general population studied. The majority of cases (60.9%, 14 of 23 positive cases) were asymptomatic.

Assuntos

Infecções por HIV/epidemiologia , Mineração/estatística & dados numéricos , Migrantes/estatística & dados numéricos , Infecções Assintomáticas/epidemiologia , Brasil/epidemiologia , Feminino , Infecções por HIV/diagnóstico , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/epidemiologia , HIV-1 , Humanos , Ferro , Masculino , Prevalência

RESUMO

A resistência às drogas antirretrovirais resulta da incompleta supressão da replicação do HIV-1. O presente estudo caracterizou o perfil de resistência genotípica aos antirretrovirais (ARV) em amostras sorológicas de 127 pacientes HIV positivos, originárias dos Estados do Amazonas e Pará, Região Norte do Brasil, no período de 2002 a 2006. As amostras TM foram submetidas ao teste de resistência pelo kit ViroSeq Genotyping System. Considerando as informações genéticas obtidas das regiões da protease e / ou transcriptase reversa do HIV-1, a mutação M184V (81,1 per cent) foi a mais associada aos inibidores nucleosídicos da transcriptase reversa (ITRN), em indivíduos usando ARV no Estado do Pará, e a mutaçãoT215F/Y (56,3 per cent) em indivíduos do Estado do Amazonas. A mutação K103N foi a mais prevalente (33,5 per cent) para os inibidores não nucleosídicos da transcriptase reversa (ITRNN) em ambos os Estados. Para o gene da protease a mutação minor L63P (65,3 per cent) apresentou-se como a mais frequente em ambos os Estados...

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Resistance to antiretroviral drugs results from the incomplete suppression of HIV-1 replication. The present study characterized the profile of genotypic resistance to antiretroviral drugs (ARVs) in serum samples from 127 HIV-positive patients from the States of Amazonas and Pará, in Northern Brazil, from 2002 to 2006. The samples were tested for TM resistance using the ViroSeq Genotyping System kit. Based on the genetic information obtained from the HIV-1 protease (PR) and / or reverse transcriptase (RT) genes, the M184V mutation (81.1 per cent) was the most frequently associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs) in individuals using ARVs in Pará, while the T215F/Ymutation (56.3 per cent) was the most frequently associated with resistance in individuals from Amazonas...

Assuntos

Masculino , Feminino , Humanos , HIV-1 , Genótipo , Mutação/genética , Resistência a Medicamentos