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PURPOSE: This case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil. METHODS: We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the Americas and Europe, Asia, and Africa. RESULTS: In the Americas, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Europe, Asia, and Africa, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved. CONCLUSION: This comparison underscores the importance of regional and immunological factors in diagnosing and managing this neglected infectious disease.
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Leishmaniose Mucocutânea , Humanos , Masculino , Leishmaniose Mucocutânea/patologia , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/tratamento farmacológico , Adulto , Infecções por HIV/complicações , Feminino , Pessoa de Meia-Idade , Doenças da Boca/patologia , Doenças da Boca/parasitologiaRESUMO
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 MESSAGES: HCV 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.
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Coinfecção , Vesículas Extracelulares , Infecções por HIV , Hepatite C , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Hepacivirus/genética , Hepacivirus/metabolismo , Coinfecção/genética , Coinfecção/patologia , HIV/genética , HIV/metabolismo , Infecções por HIV/complicações , Infecções por HIV/genética , Hepatite C/complicações , Hepatite C/genética , Hepatite C/patologia , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Inflamação/patologia , Neoplasias/patologia , Fibrose , Progressão da DoençaRESUMO
OBJECTIVE: To analyze the frequent multimodal imaging features in posterior syphilitic uveitis. PURPOSE: Syphilis infection has re-emerged as a global health problem. Multimodal imaging approach has been proposed for diagnosis and follow-up; there are not previous reports dedicated to the anatomic and visual outcomes in patients diagnosed with ocular syphilis and concomitant HIV infection. METHODS: All demographic information was recovered; a complete ophthalmological examination and multimodal imaging evaluation (retinal fluorescein angiography (FA), autofluorescence (AF), optical coherence tomography (OCT)) were performed on initial visit and 1 month after antibiotic therapy. RESULTS: 18 eyes of 9 patients were included. The most frequent features observed were: Hyperfluorescence on optic disk on FA, Hyperautofluorescence punctate pattern on AF, Vitritis on SD-OCT. After treatment, there was a functional and anatomical improvement. CONCLUSION: Ocular syphilis represents a diagnostic challenge. Multimodal imaging approach allows identification of structural changes, follow-up and early detection of complications.
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Men who have sex with men (MSM) are disproportionately affected by syphilis, HIV, and syphilis/HIV coinfection. Antiretroviral therapy (ART) prevents HIV transmission but does not impede the spread or acquisition of syphilis. Information about syphilis/HIV coinfection among MSM is scarce. We aimed to determine the prevalence of syphilis/HIV coinfection in a national sample of MSM who attend meeting places (such as movies, clubs, gay bars, saunas, shopping malls, and others referred to by the same MSM participants of the study) in Mexico to evaluate factors associated with syphilis, and to compare the prevalence rates of syphilis between the current survey and DGE data. We performed a laboratory diagnosis to determine the rates of syphilis and HIV among the included MSM. The national and regional prevalence of syphilis was calculated. HIV and coinfection prevalence were determined only for the survey. All prevalence rates included 95%CIs. Descriptive, bivariate, and multivariate analyses were performed. The national prevalence rates of syphilis, HIV, and coinfection were 15.2%, 10.2%, and 5.7%, respectively. The region with the highest prevalence rate was Mexico City (39.4%). The center region, minimal "goods" (i.e., a minimal number of material possessions such as a car or dryer, etc., which served as a proxy for low economic income level), use of "inhalant drugs", "HIV infection", "sexual intercourse" only with men, "rewarded sex", and "youngest age at first sexual encounter or debut" were risk factors for syphilis. In general, regional prevalence of syphilis was higher in the survey (2013) and DGE data from 2019 than in the DGE data from 2013. Similar to other countries, Mexico needs to assess elements around not only syphilis and HIV infections but also syphilis/HIV coinfection, and preventive measures focusing on MSM are needed.
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INTRODUCTION: The objective of the present study was to describe the clinical and epidemiological aspects of recently acquired hepatitis C virus (HCV) infection and the frequency of its spontaneous clearance in a people living with the human immunodeficiency virus (PLWH) cohort. METHODS: We reviewed the medical records from all PLWH at the human immunodeficiency virus (HIV) outpatient reference clinic affiliated with the University of São Paulo, Brazil, and identified, by immunoassays and RNA-PCR individuals who acquired HCV infection between January 2015 and December 2017. The factors associated with subsequent spontaneous clearance of the infection in this group were identified and analyzed. RESULTS: Among 3143 PLWH individuals, 362 (11.5%) were coinfected with HCV. Forty-eight (13.2%) of these subjects first became HCV-positive between January 2015 and December 2017. Spontaneous HCV clearance was documented in 23 individuals (47.9%). The majority of this latter group were male (83.3%), and the median age was 31 years (23-39). The main risk group for HCV acquisition was men who had sex with men (MSM) (89.5%). In a multivariate analysis, only an elevated CD4+ T lymphocyte count at the time of seroconversion was found to be associated with subsequent HCV clearance (p = 0.025). CONCLUSIONS: In HIV-infected individuals in Sao Paulo, Brazil, most cases of recent HCV transmission were by sexual exposure. In PLWH, particularly in MSM, the individual's CD4+ T lymphocyte count is a determinant of whether an acquired HCV infection will be prolonged or will spontaneously clear.
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Soropositividade para HIV , Hepatite C , Minorias Sexuais e de Gênero , Humanos , Masculino , Feminino , Adulto , Hepacivirus , Brasil/epidemiologia , Homossexualidade Masculina , Hepatite C/complicações , Hepatite C/epidemiologiaRESUMO
RESUMEN La coinfección por leishmaniasis visceral y VIH es una preocupación mundial debido al ascenso progresivo en los últimos años, en varias regiones del mundo. La progresión de ambas enfermedades conducen al deterioro del sistema inmune, y como resultado, al fracaso terapéutico. El presunto estudio tiene como objetivo describir las características clínico-epidemiológicas de pacientes coinfectados con el virus de inmunodeficiencia humana y leishmaniasis visceral que acuden al Instituto de Medicina Tropical, en el periodo del 2016 al 2020. Es un estudio observacional, descriptivo, de corte transversal, utilizando registros médicos de pacientes con el diagnóstico de leishmaniasis visceral y VIH. Se incluyeron 51 pacientes coinfectados, entre 19 y 65 años, 42 del sexo masculino (82,3 %); 37 procedentes del área Central. Los hallazgos clínicos mas frecuentes fueron el decaimiento del estado general y la fiebre. La mayoría de los pacientes tuvieron un recuento bajo de linfocitos tCD4 y valores elevados de carga viral de VIH. Nuestro trabajo contribuye a conocer el perfil epidemiológico de pacientes coinfectados para mejorar el diagnóstico temprano y consecuentemente el tratamiento médico precoz.
ABSTRACT Co-infection by visceral leishmaniasis and HIV is a global concern due to the progressive rise in recent years, in various regions of the world. The progression of both diseases leads to the deterioration of the immune system, and as a result, to therapeutic failure. The presumed study aims to describe the clinical-epidemiological characteristics of patients co-infected with the human immunodeficiency virus and visceral leishmaniasis who attend the Institute of Tropical Medicine, in the period from 2016 to 2020. It is an observational, descriptive, cross-sectional study, using medical records of patients diagnosed with visceral leishmaniasis and HIV. 51 coinfected patients were included, between 19 and 65 years old, 42 male (82.3%); 37 from the Central area. The most frequent clinical findings were a weakness and fever. Most of the patients had a low tCD4 lymphocyte count and high HIV viral load values. Our study contributes to knowing the epidemiological profile of coinfected patients to improve early diagnosis and consequently early medical treatment.
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Background: Host genetic factors play a major role with respect to susceptibility to infections. Many polymorphisms of the Toll-like receptors (TLRs), members of the innate immune response, are directly associated with the clinical outcomes following infection. The 2848 G/A variant (rs352140) of the TLR9 gene is associated with increased TLR9 expression. However, the impact of the genotypes of this SNP on HIV+, HCV+, and HCV+/HIV+ individuals is still debated. Materials and Methods: This study investigated the 2848 G/A polymorphism in HCV infection, HIV infection, and HCV/HIV co-infection in a large sample of Brazilians (n = 1,182). Groups were initially compared without considering stratification by ethnicity and subsequently stratifying individuals between whites and non-whites. Results: Considering non-white individuals, a significant difference between the HIV+/HCV+ group and controls was observed with the GG genotype serving as a protective factor (p = 0.023). Additionally, significant allelic differences were observed between the HCV+ group and controls (p = 0.042); between the HIV+/HCV+ group and controls (p = 0.011); and between the HIV+/HCV+ group and HIV+ individuals (p = 0.047). However, all significant results were lost following adjustment for multiple comparisons (p > 0.05). Conclusion: Although our initial results indicated a potential influence of the rs352140 genotype on host altered susceptibility to viral infections, following correction for multiple comparisions the standard (p < 0.05) for statistical association was lost. This may be due to insufficient sample size as we were examining many different associations. Thus, a larger study is warranted to further pursue this topic.
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Infecções por HIV , Hepatite C , Predisposição Genética para Doença/genética , Genótipo , Infecções por HIV/genética , Hepatite C/complicações , Hepatite C/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Receptor Toll-Like 9/genéticaRESUMO
With a widespread distribution but low prevalence worldwide, the hepatitis B virus (HBV) genotype G (HBV/G) is a recently described genotype for which the origin and biology are poorly understood. Some unique features make HBV/G the most peculiar of all genotypes. In this review, we reflect on the major milestones in HBV/G research, highlighting the main aspects of its discovery, molecular epidemiology, and virological and clinical characteristics. We also illustrate common pitfalls in the routine detection, which may lead to underestimated rates of HBV/G infection. Large-scale analysis of data from dozens of articles was further performed, with the aim of gaining comprehensive insights into the epidemiological aspects of HBV/G. Finally, we point out recent findings on HBV/G origins and discuss new perspectives regarding the evolutionary history of HBV/G and the plausibility of an African geographic re-emergence of this genotype.
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BACKGROUND: TB is still one of the leading causes of death among HIV patients. This study evaluates the effect of TB on the mortality rate, survival time, and predictors of survival in patients with AIDS living in different areas in São Paulo State (SPS). METHODS: Retrospective cohort of adolescents and adults with AIDS, diagnosed between 2003 and 2007 and followed-up until 2014. Data were obtained from the Brazilian Ministry of Health. Mortality rates were estimated by person-years. Survival analysis used the date of diagnosis as the reference for the construction of Kaplan-Meier curves. The Cox model was used for the investigation of survival-associated factors. RESULTS: A total of 35,515 patients were included, of whom 63.0% were male; 64.7% at the age group of 30 to 49 years, 64.4% were white, 12.9% co-infected with TB, and 37.6% had CD4 count above 200 cells/mm3 at diagnosis of AIDS. The 12-year survival probabilities were 74.1% and 55.7% among patients without and with TB co-infection, respectively. After adjustment for sex, age and year of diagnosis, the following exposures were independently associated with lower survival: residing in municipalities of the Interior (Hazard ratio (HR) = 1.43) and Coastal Area (HR = 1.9); illiteracy (HR = 2.61); being co-infected with TB (HR = 1.70); CD4 count below 200 cells/mm3 at AIDS diagnosis (HR = 2.31); viral load above 500 copies/ml at AIDS diagnosis (HR = 1.99); HAART1 regimen (one non-nucleoside reverse transcriptase inhibitor or boosted old protease inhibitors) (HR = 1.94). CONCLUSION: The impact of TB on survival of AIDS was heterogeneous, and affected by age, years of formal education, early AIDS diagnosis, and proper ARV treatment. These factors may not fully explain the different survival outcomes in each of the four regions within the same state. These results may subsidize focused interventions and public health policies conveying specific needs in each of the areas.
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Síndrome da Imunodeficiência Adquirida , Coinfecção , Infecções por HIV , Tuberculose , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Coortes , Coinfecção/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologiaRESUMO
Most persons living with HIV (PLWH) experience a significant restoration of their immunity associated with successful inhibition of viral replication after antiretroviral therapy (ART) initiation. Nevertheless, with the robust quantitative and qualitative restoration of CD4+ T-lymphocytes, a fraction of patients co-infected with tuberculosis develop immune reconstitution inflammatory syndrome (TB-IRIS), a dysregulated inflammatory response that can be associated with significant tissue damage. Several studies underscored the role of adaptive immune cells in IRIS pathogenesis, but to what degree T lymphocyte activation contributes to TB-IRIS development remains largely elusive. Here, we sought to dissect the phenotypic landscape of T lymphocyte activation in PLWH coinfected with TB inititating ART, focusing on characterization of the profiles linked to development of TB-IRIS. We confirmed previous observations demonstrating that TB-IRIS individuals display pronounced CD4+ lymphopenia prior to ART initiation. Additionally, we found an ART-induced increase in T lymphocyte activation, proliferation and cytotoxicity among TB-IRIS patients. Importantly, we demonstrate that TB-IRIS subjects display higher frequencies of cytotoxic CD8+ T lymphocytes which is not affected by ART. Moreover, These patients exhibit higher levels of activated (HLA-DR+) and profilerative (Ki-67+) CD4+ T cells after ART commencenment than their Non-IRIS counterparts. Our network analysis reveal significant negative correlations between Total CD4+ T cells counts and the frequencies of Cytotoxic CD8+ T cells in our study population which could suggest the existance of compensatory mechanisms for Mtb-infected cells elimination in the face of severe CD4+ T cell lymphopenia. We also investigated the correlation between T lymphocyte activation profiles and the abundance of several inflammatory molecules in plasma. We applied unsupervised machine learning techniques to predict and diagnose TB-IRIS before and during ART. Our analyses suggest that CD4+ T cell activation markers are good TB-IRIS predictors, whereas the combination of CD4+ and CD8+ T cells markers are better at diagnosing TB-IRIS patients during IRIS events Overall, our findings contribute to a more refined understanding of immunological mechanisms in TB-IRIS pathogenesis that may assist in new diagnostic tools and more targeted patient management.
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Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome Inflamatória da Reconstituição Imune/imunologia , Ativação Linfocitária , Subpopulações de Linfócitos T/imunologia , Tuberculose/imunologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Biomarcadores , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citotoxicidade Imunológica , Humanos , Síndrome Inflamatória da Reconstituição Imune/sangue , Síndrome Inflamatória da Reconstituição Imune/etiologia , Imunofenotipagem , Linfopenia/etiologia , Linfopenia/imunologia , Mycobacterium tuberculosis/imunologia , Estudos Observacionais como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estudos Retrospectivos , Tuberculose/complicaçõesRESUMO
Coinfection with the human immunodeficiency virus (HIV) and Leishmania impairs immune responses, increases treatment failure and relapse rates in patients with American tegumentary leishmaniasis (ATL), as well as visceral leishmaniasis (VL). There is insufficient data on the treatment, relapse, and secondary prophylaxis in patients coinfected with HIV/Leishmania in Brazil. This study investigated patients with HIV/ATL and HIV/VL to describe the outcome of leishmaniasis in patients assisted at a referral hospital of Brazilian midwestern region. Patients with HIV/ATL (n = 21) mainly presented cutaneous diseases (76.2%) with an overall relapse rate of 28.57% after treatment, whereas HIV/VL (n = 28) patients accounted for 17.5% of the cases. The counts of CD4+ T cells and CD8+ T cells and the CD4+/CD8+ cell ratios at diagnosis or relapses were not significantly different between relapsing and non-relapsing patients. Patients with HIV/ATL or HIV/VL showed high levels of activation markers in CD4+ and CD8+ T cells. The regular use of highly active antiretroviral therapy (HAART) and viral load at the time of diagnosis did not influence the relapse rates. Relapses occurred in 36.4% (4/11) of the patients with HIV/VL receiving secondary prophylaxis and in 5.9% (1/17) of the patients who did not receive secondary prophylaxis (p = 0.06). These data are relevant for the therapeutic management of the patients coinfected with HIV/Leishmania.
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Coinfecção , Infecções por HIV , Leishmania , Leishmaniose Visceral , Leishmaniose , Linfócitos T CD8-Positivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , RecidivaRESUMO
The diagnosis of visceral leishmaniasis (VL) has improved with the search of novel antigens; however, their performance is limited when samples from VL/human immunodeficiency virus (HIV)-coinfected patients are tested. In this context, studies conducted to identify more suitable antigens to detect both VL and VL/HIC coinfection cases should be performed. In the current study, phage display was performed using serum samples from healthy subjects and VL, HIV-infected and VL/HIV-coinfected patients; aiming to identify novel phage-exposed epitopes to be evaluated with this diagnostic purpose. Nine non-repetitive and valid sequences were identified, synthetized and tested as peptides in enzyme-linked immunosorbent assay experiments. Results showed that three (Pep2, Pep3 and Pep4) peptides showed excellent performance to diagnose VL and VL/HIV coinfection, with 100% sensitivity and specificity values. The other peptides showed sensitivity varying from 50.9 to 80.0%, as well as specificity ranging from 60.0 to 95.6%. Pep2, Pep3 and Pep4 also showed a potential prognostic effect, since specific serological reactivity was significantly decreased after patient treatment. Bioinformatics assays indicated that Leishmania trypanothione reductase protein was predicted to contain these three conformational epitopes. In conclusion, data suggest that Pep2, Pep3 and Pep4 could be tested for the diagnosis of VL and VL/HIV coinfection.
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Bacteriófagos , Coinfecção , Infecções por HIV , Leishmaniose Visceral , Coinfecção/diagnóstico , Epitopos , HIV , Infecções por HIV/diagnóstico , Humanos , Leishmaniose Visceral/diagnósticoRESUMO
La tuberculosis (TB) es la infección oportunista más frecuente en pacientes infectados por el VIH, con impactos bidireccionales en el paciente: al aumentar la carga viral, la TB acelera la progresión de la infección por VIH a SIDA y, con ello, a la muerte. A su vez, El VIH dificulta el diagnóstico y tratamiento de la TB y favorece el desarrollo de diversas complicaciones clínicas. Al considerar que (1) sólo las dos terceras partes de la población seropositiva en el mundo tienen acceso a terapia antiretroviral; que (2) la tercera parte de fallecidos por SIDA en 2019 estaban también diagnosticados con TB; que (3) a nivel global el riesgo de morir por TB se duplica en el individuo con diagnóstivo de VIH positivo; y que (4) en las Américas, únicamente el 61% de las personas con TB-VIH reciben tratamiento antiretroviral, dejando tres veces más muertes y dos veces más pérdida en el seguimiento en los coinfectados, se evidencia una realidad preocupante sobre los resultados de las actuales políticas de tratamiento para la coinfección TB-VIH, haciendo necesario explorar sus bases, alcance, y metodologías en América y en Ecuador(AU)
Tuberculosis (TB) is the most frequent opportunistic infection in HIV-infected patients, with two-way impacts on the patient: by increasing the viral load, TB accelerates the progression from HIV infection to AIDS and, with it, to the death. In turn, HIV makes the diagnosis and treatment of TB difficult and favors the development of various clinical complications. Considering that (1) only two thirds of the HIV-positive population in the world have access to antiretroviral therapy; that (2) a third of those who died from AIDS in 2019 were also diagnosed with TB; that (3) globally, the risk of dying from TB is doubled in the individual with a positive HIV diagnosis; and that (4) in the Americas, only 61% of people with TB-HIV receive antiretroviral treatment, leaving three times more deaths and two times more loss to follow-up in those who are coinfected, there is a worrying reality about the results of current treatment policies for TB-HIV coinfection, making it necessary to explore its bases, scope, and methodologies in America and Ecuador(AU)
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Humanos , Masculino , Feminino , Tuberculose/tratamento farmacológico , HIV , Infecções por HIVRESUMO
BACKGROUND: Human pegivirus (HPgV)-formerly known as GBV-C-is a member of the Flaviviridae family and belongs to the species Pegivirus C. It is a non-pathogenic virus and is transmitted among humans mainly through the exposure to contaminated blood and is often associated with human immunodeficiency virus (HIV) infection, among other viruses. This study aimed to determine the prevalence of HPgV viremia, its association with HIV and clinical epidemiological factors, as well as the full-length sequencing and genome characterization of HPgV recovered from blood donors of the HEMOPA Foundation in Belém-PA-Brazil. METHODS: Plasma samples were obtained from 459 donors, tested for the presence of HPgV RNA by the RT-qPCR. From these, a total of 26 RT-qPCR positive samples were submitted to the NGS sequencing approach in order to obtain the full genome. Genome characterization and phylogenetic analysis were conducted. RESULTS: The prevalence of HPgV was 12.42%. We observed the highest prevalences among donors aged between 18 and 30 years old (16.5%), with brown skin color (13.2%) and men (15.8%). The newly diagnosed HIV-1 prevalence was 26.67%. The HPgV genotype 2 (2a and 2b) was identified. No data on viral load value was found to corroborate the protective effect of HPgV on HIV evolution. CONCLUSIONS: This study provided information regarding the HPgV infection among blood donors from HEMOPA Foundation. Furthermore, we genetically characterized the HPgV circulating strains and described by the first time nearly complete genomes of genotype 2 in Brazilian Amazon.
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Doadores de Sangue , Infecções por Flaviviridae/epidemiologia , Vírus GB C/genética , Pegivirus/genética , RNA Viral/sangue , Viremia/epidemiologia , Adolescente , Adulto , Doadores de Sangue/estatística & dados numéricos , Brasil/epidemiologia , Estudos Transversais , Feminino , Infecções por Flaviviridae/virologia , Vírus GB C/classificação , Vírus GB C/isolamento & purificação , Genoma Viral , Genótipo , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pegivirus/classificação , Pegivirus/isolamento & purificação , Filogenia , Prevalência , RNA Viral/genética , Carga Viral , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
In a hepatitis C virus (HCV)/HIV-positive Brazilian cohort, evaluate the safety and efficacy of HCV DAAs, the frequency of resistance substitutions in the HCV NS5A and NS5B genes and identify predictors of treatment failure. Retrospective multicenter study of HCV/HIV patients treated with sofosbuvir (SOF)-based regimens at 10 reference centers in Brazil. Clinical and virological data were collected. Genetic diversity in the NS5A and NS5B genes was assessed by direct nucleotide sequencing. The primary outcome was sustained virological response (SVR) 12 weeks after DAA completion. Of 643HCV/HIV patients analyzed, 74.7% were male, median CD4+ T cell count was 617cells/mm3, 90% had an undetectable HIV viral load. HCV genotype 1 was detected in 80.2%, and 60% were taking at least 1 medication other than antiretroviral drugs during their DAA therapy. Cirrhosis was present in 42%. An SOF/daclatasvir (DCV) regimen was used in most patients (98%). The frequency of NS5A polymorphisms associated with clinically relevant resistance to DCV was 2%; no relevant NS5B variants were identified. The SVR12 rate was 92.8% in an intention to treat (ITT) analysis and 96% in a modified ITT (m-ITT) analysis. AE occurred in 1.6% of patients. By multivariate analysis, therapeutic failure was associated, in the m-ITT analysis, with concomitant use of anticonvulsant drugs (P=.001), age (P=.04), and female gender (P=.04). SOF/DCV regimens were associated with a high SVR rate in an HCV/HIV population. The use of concurrent anticonvulsant drugs and DAAs decreases the chances of achieving an SVR
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Humanos , Antivirais/uso terapêutico , HIV , Hepatite C/tratamento farmacológico , Coinfecção/tratamento farmacológicoRESUMO
Chronic hepatitis C virus (HCV) infection induces liver damage and the HCV/Human Immunodeficiency Virus (HIV)-coinfection may further contribute to its progression. The HLA-G molecule inhibits innate and adaptive immunity and may be deleterious for chronically virus-infected cells. Thus we studied 204 HCV-mono-infected patients, 142 HCV/HIV-coinfected patients, 104 HIV-mono-infected patients and 163 healthy subjects. HLA-G liver expression was similarly induced in HCV and HCV/HIV specimens, increasing with advanced fibrosis and necroinflammatory activity, and with increased levels of liver function-related enzymes. Plasma soluble HLA-G (sHLA-G) levels were higher in HCV/HIV patients compared to HCV, HIV and to healthy individuals. sHLA-G continued to be higher in coinfected patients even after stratification of samples according to degree of liver fibrosis and necroinflammatory activity when compared to mono-infected patients. Some HLA-G gene haplotypes differentiated patient groups and presented few associations with liver and plasma HLA-G expression. HLA-G thus may help to distinguish patient groups.
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Infecções por HIV/imunologia , Antígenos HLA-G/genética , Antígenos HLA-G/metabolismo , Hepatite C Crônica/imunologia , Fígado/metabolismo , Adulto , Coinfecção , Feminino , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , HIV-1/imunologia , Haplótipos/genética , Hepacivirus/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Estudos RetrospectivosRESUMO
The co-infection between visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) has increased in several countries in the world. The current serological tests are not suitable since they present low sensitivity to detect the most of VL/HIV cases, and a more precise diagnosis should be performed. In this context, in the present study, an immunoproteomics approach was performed using Leishmania infantum antigenic extracts and VL, HIV and VL/HIV patients sera, besides healthy subjects samples; aiming to identify antigenic markers for these clinical conditions. Results showed that 43 spots were recognized by antibodies in VL and VL/HIV sera, and 26 proteins were identified by mass spectrometry. Between them, ß-tubulin was expressed, purified and tested in ELISA experiments as a proof of concept for validation of our immunoproteomics findings and results showed high sensitivity and specificity values to detect VL and VL/HIV patients. In conclusion, the identified proteins in the present work could be considered as candidates for future studies aiming to improvement of the diagnosis of VL and VL/HIV co-infection.
Assuntos
Coinfecção/diagnóstico , Infecções por HIV/diagnóstico , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Proteômica/métodos , Proteínas de Protozoários/análise , Adulto , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Visceral leishmaniasis (VL) is a public health threat for several tropical countries, including Brazil. Therapy failures and relapses aggravate VL morbidity and mortality. Our study aimed at identifying predictors of relapse and thus contributes to directing therapeutic options and patient follow-up. METHODS: A nonconcurrent cohort of 571 subjects who completed successful therapy for VL in the city of Bauru, São Paulo State, Brazil, was followed for 24 months in order to identify the incidence and predictors of relapse. Extensive review of medical charts and laboratory files was conducted. Univariate and multivariable Cox regression models were used to identify predictors for the outcome of interest. A hierarchical strategy was used for variable selection in multivariable models. RESULTS: Relapses occurred in 6.8% of treated subjects, after a median of 6 months (interquartile range, 4-9). In a comprehensive multivariable model, relapse was associated with: HIV-coinfection (hazard ratio [HR], 7.47; 95% confidence interval [CI], 2.58-21.55); the presence of lower limb edema (HR, 6.06; 95%CI, 1.38-26.77) and low platelet count upon admission (HR for platelet count × 1000, 0.99; 95%CI, 0.98-0.99) ; and secondary pneumonia (HR, 5.49; 95%CI, 1.49-20.18). On the other hand, therapy with Liposomal Amphotericin (as opposed to Antimoniate) was not independently associated with relapse (HR, 5.97; 95%CI, 0.63-56.29). CONCLUSION: Besides reinforcing the impact of HIV coinfection on the outcome of VL, our study points to clinical and laboratory findings that characterize patients who were more likely to relapse. Those groups should be more closely followed, and possibly could benefit from novel therapeutic options.
Assuntos
Leishmaniose Visceral/tratamento farmacológico , Adolescente , Adulto , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Coinfecção , Edema/epidemiologia , Feminino , Infecções por HIV/complicações , Humanos , Lactente , Recém-Nascido , Leishmaniose Visceral/complicações , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
This study aimed to identify Candida spp. collected from oral mucosa and maintained in culture collections, correlating the findings with the medical history of patients and comparing with data from the literature over the past five years. Seven hundred and eleven oral Candida spp. isolates, collected between 2013 and 2017, were selected and identified using traditional and molecular methods. In addition, a literature review was performed with the key words: "Oral", "Candida" and "Yeast". Seven species of the genus Candida: were identified C. albicans(73.3%); C. tropicalis (9.3%); C. parapsilosis (8.2%); C. glabrata (3.9%); C. guilliermondii(2.8%); C. krusei (1.7%) and C. lusitaniae (0.3%). The strains identified as C. albicans were submitted to molecular methods using specific primers and of these, 5.8% were identified as C. dubliniensis strains. The greatest diversity of strains was found in patients presenting no systemic diseases or HIV +, while the highest percentage of strains of Candidanon-albicanswere observed in cancer patients. This study reports a representative distribution of Candidaspecies among individuals exhibiting distinct clinical conditions, in order to contribute to the design of future research on details of aspects involved in the infections caused by these microorganisms. The correct identification of oral Candida strains contributes to a realistic epidemiological approach and future clinical protocols against these pathogens
Assuntos
Candida , HIV , Mucosa Bucal , NeoplasiasRESUMO
Tuberculosis (TB) is the most common comorbidity and the leading cause of death among HIV-infected individuals. Although the combined antiretroviral therapy (cART) during TB treatment improves the survival of TB/HIV patients, the occurrence of immune reconstitution inflammatory syndrome (IRIS) in some patients poses clinical and scientific challenges. This work aimed to evaluate blood innate lymphocytes during therapeutic intervention for both diseases and their implications for the onset of IRIS. Natural killer (NK) cells, invariant NKT cells (iNKT), γδ T cell subsets, and in vitro NK functional activity were characterized by multiparametric flow cytometry in the following groups: 33 TB/HIV patients (four with paradoxical IRIS), 27 TB and 25 HIV mono-infected subjects (prior to initiation of TB treatment and/or cART and during clinical follow-up to 24 weeks), and 25 healthy controls (HC). Concerning the NK cell repertoire, several activation and inhibitory receptors were skewed in the TB/HIV patients compared to those in the other groups, especially the HCs. Significantly higher expression of CD158a (p = 0.025), NKp80 (p = 0.033), and NKG2C (p = 0.0076) receptors was detected in the TB/HIV IRIS patients than in the non-IRIS patients. Although more NK degranulation was observed in the TB/HIV patients than in the other groups, the therapeutic intervention did not alter the frequency during follow-up (weeks 2-24). A higher frequency of the γδ T cell population was observed in the TB/HIV patients with inversion of the Vδ2+/Vδ2- ratio, especially for those presenting pulmonary TB, suggesting an expansion of particular γδ T subsets during TB/HIV co-infection. In conclusion, HIV infection impacts the frequency of circulating NK cells and γδ T cell subsets in TB/HIV patients. Important modifications of the NK cell repertoire were observed after anti-TB treatment (week 2) but not during the cART/TB follow-up (weeks 6-24). An increase of CD161+ NK cells was related to an unfavorable outcome. Despite the low number of cases, a more preserved NK cell profile was detected in IRIS patients previous to treatment, suggesting a role for these cells in IRIS onset. Longitudinal evaluation of the NK repertoire showed the impact of TB treatment and implicated these cells in TB pathogenesis in TB/HIV co-infected patients.