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1.
Rev Bras Epidemiol ; 22Suppl 1(Suppl 1): e190008, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31576984

RESUMO

OBJECTIVE: To analyze the distribution of health care services for viral hepatitis and reported cases of viral hepatitis according to the health regions of Northern Brazil. METHOD: It is an evaluative, descriptive and quantitative research considering viral hepatitis care services and reported cases in the Northern region of Brazil, using data collected from the National Registry of Health Establishments and the Notifiable Diseases Information System. Descriptive statistics and georeferencing, through software, were used to demonstrate the spatial distribution of services and reported cases. RESULTS: Viral hepatitis health services are distributed in a differentiated way; rapid tests are capillaries in the states; confirmatory tests and treatment are performed in some health regions, with a greater grouping of services in the capitals and their surroundings. Cases were reported across all regions, with areas of higher concentration near services. CONCLUSION: The availability of services can favor access to prevention, diagnosis and monitoring of cases. However, organizational peculiarities of the health system and services highlight fragilities that have repercussions on the access and entirety of viral hepatitis care.


Assuntos
Acesso aos Serviços de Saúde/estatística & dados numéricos , Serviços de Saúde/estatística & dados numéricos , Hepatite Viral Humana/epidemiologia , Brasil/epidemiologia , Notificação de Doenças/estatística & dados numéricos , Geografia , Pesquisa sobre Serviços de Saúde , Hepatite Viral Humana/diagnóstico , Humanos , Fatores Socioeconômicos , Carga Viral/estatística & dados numéricos
2.
N Engl J Med ; 381(13): 1240-1247, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31509667

RESUMO

The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown. CCR5 is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because CCR5-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated CCR5 persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with CCR5 ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of CCR5 disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.).


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Infecções por HIV/terapia , HIV-1 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Receptores CCR5/genética , Adulto , Antirretrovirais/uso terapêutico , Contagem de Células Sanguíneas , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Carga Viral
3.
Arch Virol ; 164(11): 2735-2745, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486907

RESUMO

Koala retrovirus (KoRV) is unique among endogenous retroviruses because its endogenization is still active. Two major KoRV subtypes, KoRV-A and B, have been described, and KoRV-B is associated with disease and poses a health threat to koalas. Here, we investigated the co-prevalence of KoRV-A and KoRV-B, detected by type-specific PCR and sequencing, and their impact on the health of koalas in three Japanese zoos. We also investigated KoRV proviral loads and found varying amounts of genomic DNA (gDNA) in peripheral blood mononuclear cells (PBMCs). We found that 100% of the koalas examined were infected with KoRV-A and 60% (12/20) were coinfected with KoRV-B. The KoRV-A sequence was highly conserved, whereas the KoRV-B sequence varied among individuals. Interestingly, we observed possible vertical transmission of KoRV-B in one offspring in which the KoRV-B sequence was similar to that of the father but not the mother. Moreover, we characterized the KoRV growth patterns in concanavalin-A-stimulated PBMCs isolated from KoRV-B-coinfected or KoRV-B-uninfected koalas. We quantified the KoRV provirus in gDNA and the KoRV RNA copy numbers in cells and culture supernatants by real-time PCR at days 4, 7, and 14 post-seeding. As the study population is housed in captivity, a longitudinal study of these koalas may provide an opportunity to study the transmission mode of KoRV-B. In addition, we characterized KoRV isolates by infecting tupaia cells. The results suggested that tupaia may be used as an infection model for KoRV. Thus, this study may enhance our understanding of KoRV-B coinfection and transmission in the captive koalas.


Assuntos
Retrovirus Endógenos/genética , Gammaretrovirus/patogenicidade , Phascolarctidae/virologia , Infecções por Retroviridae/epidemiologia , Infecções por Retroviridae/veterinária , Animais , Animais de Zoológico/virologia , Linhagem Celular , Coinfecção/veterinária , Coinfecção/virologia , Retrovirus Endógenos/classificação , Retrovirus Endógenos/isolamento & purificação , Feminino , Gammaretrovirus/classificação , Gammaretrovirus/genética , Gammaretrovirus/isolamento & purificação , Japão/epidemiologia , Masculino , Provírus/genética , Infecções por Retroviridae/virologia , Tupaia/virologia , Carga Viral
4.
MMWR Morb Mortal Wkly Rep ; 68(30): 658-663, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31369522

RESUMO

Reducing HIV-related morbidity and mortality, and effectively eliminating HIV transmission risk, depends on use of antiretroviral therapy (ART) to achieve and maintain viral load suppression (VLS)* (1,2). By 2020, sub-Saharan African countries are working to achieve VLS among 90% of persons using ART and 73% of all persons living with HIV infection (1). In Tanzania, a country with 1.4 million persons with HIV infection, 49.6% of HIV-positive persons aged 15-49 years had achieved VLS in 2017, including only 21.5% of men and 44.6% of women aged 25-29 years (3). To identify interventions that might increase VLS in Tanzania, and reduce VLS-associated sex and age-group disparities, the Bukoba Combination Prevention Evaluation (BCPE) scaled up new HIV testing, linkage to care, and retention on ART interventions throughout Bukoba Municipal Council (Bukoba), Tanzania, during October 2014-March 2017 (4,5). Located on the western shore of Lake Victoria, Bukoba is a mixed urban and rural municipality of 150,000 persons and capital of Kagera Region. Of the 31 regions of Tanzania, Kagera has the fourth highest prevalence of HIV infection (6.8%) among residents aged 15-49 years (3). CDC analyzed data from BCPE preintervention and postintervention surveys and found that VLS prevalence among HIV-positive Bukoba residents aged 18-49 years increased approximately twofold overall (from 28.6% to 64.8%) and among women (33.3% to 67.8%) and approximately threefold among men (20.5% to 59.1%) and young adults aged 18-29 years (15.6% to 56.7%). During 2017, BCPE facility-based testing and linkage interventions were approved as new service delivery models by the Tanzania Ministry of Health, Community Development, Gender, Elderly and Children (4,5). After a successful rollout to 208 facilities in 11 regions in 2018, BCPE interventions are being scaled up in all regions of Tanzania in 2019 with support from the United States President's Emergency Plan for AIDS Relief (PEPFAR).†.


Assuntos
Infecções por HIV/prevenção & controle , Carga Viral/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tanzânia , Adulto Jovem
5.
MMWR Morb Mortal Wkly Rep ; 68(30): 653-657, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31369525

RESUMO

During 2016, 6% of persons in the United States who received a diagnosis of human immunodeficiency virus (HIV) infection had their HIV infection attributed to injection drug use (1). Injection practices and sexual behaviors among HIV-positive persons who inject drugs, such as injection equipment sharing and condomless sex, can increase HIV transmission risk; nationally representative estimates of the prevalences of these behaviors are lacking. The Medical Monitoring Project (MMP) is an annual, cross-sectional survey that reports nationally representative estimates of clinical and behavioral characteristics among U.S. adults with diagnosed HIV (2). CDC used MMP data to assess high-risk injection practices and sexual behaviors among HIV-positive persons who injected drugs during the preceding 12 months and compared their HIV transmission risk behaviors with those of HIV-positive persons who did not inject drugs. During 2015-2017, approximately 10% (weighted percentage estimate) of HIV-positive persons who injected drugs engaged in distributive injection equipment sharing (giving used equipment to another person for use); nonsterile syringe acquisition and unsafe disposal methods were common. Overall, among HIV-positive persons who injected drugs, 80% received no treatment, and 57% self-reported needing drug or alcohol treatment. Compared with HIV-positive persons who did not inject drugs, those who injected drugs were more likely to have a detectable viral load (48% versus 35%; p = 0.008) and engage in high-risk sexual behaviors (p<0.001). Focusing on interventions that reduce high-risk injection practices and sexual behaviors and increase rates of viral suppression might decrease HIV transmission risk among HIV-positive persons who inject drugs. Successful substance use treatment could also lower risk for transmission and overdose through reduced injection.


Assuntos
Infecções por HIV/diagnóstico , Assunção de Riscos , Comportamento Sexual/psicologia , Abuso de Substâncias por Via Intravenosa/psicologia , Infecções por HIV/transmissão , Humanos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Estados Unidos/epidemiologia , Carga Viral/estatística & dados numéricos
6.
Zhonghua Fu Chan Ke Za Zhi ; 54(7): 458-463, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31365958

RESUMO

Objective: To explore the relationship between cervical lesions and high risk HPV (HR-HPV) viral load reflected by the cycle threshold (Ct) values of Cobas 4800 HPV (Cobas 4800) system. Methods: From August 2016 to September 2017, 7 000 women from Shenzhen, were recruited for cervical cancer screening with Cobas 4800 system and cytology co-test. Colposcope biopsies were performed on women who were positive of HPV 16, 18, and positive of HPV types other than 16,18 with cytology [≥ atypical squamous cell of undetermined signification (ASCUS)], or HPV negative but abnormal of cytology [≥ low grade squamous intraepithelial lesion (LSIL)]. The Ct values of HPV 16, 18 and all combined other types coming from Cobas 4800 system were used as an indicator of viral load to analyze the relationship between type-specific HPV load and the cervical lesions. Results: (1) Among the 7 000 screening women, 370 cases were positive for cervical cancer screening, 325 of them underwent colposcope biopsies, and coloposcopy referred rate was 87.8% (325/370). Among 325 women undergoing cervical biopsy, pathological diagnosis was 119 cases of normal cervical cervix, 151 cases of LSIL, and 55 cases of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL(+); including 53 cases of HSIL, 1 case of cervical adenocarcinoma, and 1 case of cervical squamous cell carcinoma). (2) The Ct value of HPV 16 was inversely correlated with the upgrading of the lesions (r=-0.617, P=0.000), and significant different among normal cervix,LSIL and HSIL(+) (35.4±4.5 vs 31.0±6.0 vs 26.5±4.0; F=25.537, P=0.000). There was no correlation between Ct value of HPV 18 and cervical lesions (r=-0.021, P=0.902). The Ct value of other 12 HPV types was statistically difference among normal normal cervix, HSIL(+) and cervicitis (33.0±5.3 vs 29.9±7.2 vs 29.8±5.8; F=5.087, P=0.007). Among them, LSIL and HSIL(+) were significantly lower than normal cervix (P<0.05), but there was no significant difference between LSIL and HSIL(+) (P>0.05). Conclusion: The Ct value of HPV 16 detecting in Cobas 4800 system as an indicator of virus load obviously correlates with different grades of cervical lesions, therefore could be a reference of cervical lesion existence and an indicator of lesion prognosis.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Testes de DNA para Papilomavírus Humano/instrumentação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/virologia , Detecção Precoce de Câncer , Feminino , Testes de DNA para Papilomavírus Humano/métodos , Humanos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Carga Viral
7.
Braz J Med Biol Res ; 52(8): e8519, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389490

RESUMO

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.


Assuntos
Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Imidazóis/administração & dosagem , Transplante de Fígado/efeitos adversos , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral
9.
Mem Inst Oswaldo Cruz ; 114: e190150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31432892

RESUMO

BACKGROUND: Zika virus (ZIKV) infections reported in recent epidemics have been linked to clinical complications that had never been associated with ZIKV before. Adaptive mutations could have contributed to the successful emergence of ZIKV as a global health threat to a nonimmune population. However, the causal relationships between the ZIKV genetic determinants, the pathogenesis and the rapid spread in Latin America and in the Caribbean remain widely unknown. OBJECTIVES: The aim of this study was to characterise three ZIKV isolates obtained from patient samples during the 2015/2016 Brazilian epidemics. METHODS: The ZIKV genomes of these strains were completely sequenced and in vitro infection kinetics experiments were carried out in cell lines and human primary cells. FINDINGS: Eight nonsynonymous substitutions throughout the viral genome of the three Brazilian isolates were identified. Infection kinetics experiments were carried out with mammalian cell lines A549, Huh7.5, Vero E6 and human monocyte-derived dendritic cells (mdDCs) and insect cells (Aag2, C6/36 and AP61) and suggest that some of these mutations might be associated with distinct viral fitness. The clinical isolates also presented differences in their infectivity rates when compared to the well-established ZIKV strains (MR766 and PE243), especially in their abilities to infect mammalian cells. MAIN CONCLUSIONS: Genomic analysis of three recent ZIKV isolates revealed some nonsynonymous substitutions, which could have an impact on the viral fitness in mammalian and insect cells.


Assuntos
Aedes/virologia , Replicação Viral , Infecção por Zika virus/virologia , Zika virus/genética , Animais , Brasil , Cercopithecus aethiops , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Filogenia , Células Vero , Carga Viral , Cultura de Vírus
10.
Mikrobiyol Bul ; 53(3): 285-296, 2019 Jul.
Artigo em Turco | MEDLINE | ID: mdl-31414630

RESUMO

BK virus (BKV) viral load quantification has a distinct role in the clinical control of BKV nephropathy and organ rejection among renal transplant recipients. In this study, it was aimed to compare BKV DNA measurement values performed with two different real-time polymerase chain reaction (PCR) methods and to determine BKV genotypes in renal transplant recipients. Totally, 150 clinical samples tested previously in two different laboratories (Lab-1 and Lab-2) from adult and pediatric renal transplantation patients were included in the study. Fifty plasma samples of 50 different patients from Lab-1, 50 plasma and 50 urine samples of 58 different patients from Lab-2 were included in the study. Viral nucleic acid extraction was performed with automatized systems in Lab-1 and Lab-2 (EZ1, Qiagen, Germany and MagNA Pure 96, Roche Diagnostics, Germany; respectively;). Real-time PCR procedure was carried out in Lab-1 with an amplification mixture of primer, probe sequences targeting VP-1 gene region using RotorGene (Qiagen, Germany) and in Lab-2 with an amplification mixture of primer, probe sequences targeting VP-2 gene region using ABI Prism 7500 (Applied Biosystems, USA). BKV genotyping was performed with multiplex PCR using primer, probe sequences for BKV genotypes I-IV. In both of the laboratories, 82 (54.6%) of the samples were found as positive, 37(24.6%) samples were found as negative and a moderate agreement was found between qualitative results of two real-time PCR methods (ƙ= 0.56, p<0.001). Median viral load values were 4.1 x 104 copies/ml (321-6 x 109) in Lab-1 and 3.3 x 105 copies/ml (224-8.3 x 1010) in Lab-2 for positive samples. According to the lineer regression analysis of quantitative results, moderate (R2= 0.52, p<0.001) and high (R2= 0.88, p<0.001) correlation was found for plasma (n= 52) and urine (n= 30) samples, respectively. Bland-Altman analysis yielded a mean difference of -0.58 log10 for all samples. For plasma samples mean difference was -0.29 log10, while it was -1.1 log10 for urine samples. In all samples, Lab-1 measurements were lower than Lab-2 measurements. A mean difference of -1.1 log10 indicated that the measurement values of Lab-2 were more higher than Lab-1 measurments with an average of 1.1 log10. Supporting this result, 71.9% of the samples had a measurement difference more than 0.5 log 10 and 29.2% of the samples had a measurement difference more than 1 log10. Only 28.1% of the samples were measured within clinically acceptable log difference range (less than 0.5 log10). BKV genotyping was performed only for 74 different patient samples with sufficient copy numbers and genotype I (81.7%), IV (15.5%), II (1.4%), I+IV (1.4%) were detected. When the results were compared; 66.6% (n= 12) of the genotype IV samples had more than 1 log10 and 83.3% of them had more than 0.5 log10 viral load measurement difference. Correlation and linear regression analyzes were insufficient for the comparison ofthe results of the two different tests. It will be appropriate for each center to monitor patients with the same test until the international BKV standard developed by the World Health Organization is optimized. The clinical correlation of the tests is limited to the currently used test. The result of incorrect BKV quantification affects the clinical decision. Measurements less than the actual value will lead to the development of BKV nephropathy, and higher measurements will lead to unnecessary allograft biopsy and unnecessary reduction of immunosuppression.


Assuntos
Vírus BK , Infecções por Polyomavirus , Reação em Cadeia da Polimerase em Tempo Real , Infecções Tumorais por Vírus , Adulto , Vírus BK/genética , Criança , DNA Viral , Genótipo , Alemanha , Humanos , Transplante de Rim , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/virologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Transplantados , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/virologia , Carga Viral
11.
Medicine (Baltimore) ; 98(32): e16357, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393344

RESUMO

Achieving and maintaining viral suppression in young adults (18-24 years) living with HIV is challenging. Overall HIV viral suppression rates are lower in young as compared to older adults. Longitudinal data provide valuable insight on dynamics of viral suppression and variables of potential influence on HIV virological failure (VF), but is scarce in young adults living with HIV on combination antiretroviral therapy (cART). We evaluated longitudinal virological outcomes of behaviorally young adults (18-24 years) living with HIV in the Netherlands over a period of 15 years.We analyzed data from the Dutch national HIV database of 816 young adults living with HIV on cART in the Netherlands from 2000 to 2015. VF was defined as 2 consecutive detectable plasma HIV-1 viral load (VL) measurements > 200 copies/ml. Generalized linear mixed model analyses were used to assess HIV VF over time and identify risk factors associated with VF.VF during the study follow-up occurred at least once in 26% of cases. The probability of experiencing VF decreased over the study period per calendar year (OR 0.78, 95% confidence interval [CI];0.72; 0.85). Factors significantly associated with VF were being infected through heterosexual contact (OR 5.20, CI 1.39;19.38) and originating from Latin America or the Caribbean (OR 6.59, CI 2.08;20.92). Smaller, yet significant risk factors for VF were being infected through a blood transfusion or a needle accident (OR9.93, CI 1.34;73.84, and having started with cART with a nadir CD4 count >500 cells/µl (OR 11.36, CI 2.03;63.48).In our large cohort of young adults, the risk of VF has diminished over 15 years. Specific subgroups were identified to be at risk for suboptimal treatment.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Antirretrovirais/administração & dosagem , Contagem de Linfócito CD4 , Grupos de Populações Continentais , Quimioterapia Combinada , Feminino , Infecções por HIV/etiologia , HIV-1 , Humanos , Estudos Longitudinais , Masculino , Países Baixos , Fatores de Risco , Comportamento Sexual , Falha de Tratamento , Carga Viral , Adulto Jovem
12.
Medicine (Baltimore) ; 98(32): e16683, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393369

RESUMO

Interferon-alpha (IFN-α) is currently the preferred antiviral treatment for children with chronic hepatitis B (CHB) aged >1-year-old. However, the evidence regarding the exact efficacy and safety in the real world is not sufficient. This study aimed to investigate the efficacy of IFN-α therapy in children with CHB and to provide a theoretical basis for practically identifying ideal antiviral therapies for CHB children.Clinical manifestations, baseline characteristics, related laboratory tests, and adverse events were retrospectively analyzed in children with CHB who visited the Children's Hospital of Fudan University, were treated with IFN-α and were followed up from January 2003 to October 2018.A total of 18 immune-active patients without advanced fibrosis were enrolled, and their average age at the start of treatment was 4.45 ±â€Š2.75 years old. IFN α-2b was administered subcutaneously by body surface area (BSA) category, based on 3 MU/m, for a median 48 weeks. Before treatment, the alanine aminotransferase (ALT) range was 81 to 409 U/L (median 158 U/L). The median hepatitis B virus (HBV)-DNA load was 9.89 × 10 IU/mL, and the HBV-DNA load varied from 3.10 × 10 to 4.56 × 10 IU/mL. The ALT levels of 17 children became normal at an average of 12 weeks during treatment, and those of 1 child became normal at 6 weeks after IFN-α withdrawal. Sixteen (88.9%, 16/18) children became HBV-DNA negative (<10 IU/mL) at an average of 24 weeks during treatment, while 1 became negative at 96 weeks after IFN-α withdrawal and 1 remained HBV-DNA positive. HBV e antigen (HBeAg) seroconversion occurred in 13 of 14 (92.9%, 13/14) HBeAg-positive patients at an average of 12 weeks during treatment. HBV s antigen (HBsAg) loss or seroconversion occurred in 4 (22.2%, 4/18) patients at an average of 21 weeks during treatment. Only mild flu-like symptoms and transient neutropenia appeared in some children at the early treatment stage. No severe abnormal results were observed in other laboratory parameters.The antiviral monotherapy of 48 weeks of IFN-α was well tolerated and good responded, which was associated with higher rates of HBeAg seroconversion and HBsAg clearance in the children in this study than in previously reported adults and pediatric patients.


Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Adolescente , Antivirais/farmacologia , Criança , Pré-Escolar , China , Estudos de Coortes , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Interferon-alfa/farmacologia , Masculino , Soroconversão/efeitos dos fármacos , Carga Viral/efeitos dos fármacos
13.
Medicine (Baltimore) ; 98(32): e16721, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393378

RESUMO

The aim of this retrospective cohort study was to compare safety, efficacy and rates and reasons of discontinuation of the 3 currently approved integrase strand transfer inhibitors (INSTIs) elvitegravir (EVG), dolutegravir (DTG), and raltegravir (RAL) in HIV-infected treatment-naïve and -experienced patients in a real-world cohort. One hundred four treatment-naïve patients were prescribed an INSTI-based combined antiretroviral therapy (cART)-regimen (first-line group) and 219 patients were switched to an INSTI-based cART-regimen from another treatment regimen (switch group) at our institution between May 2007 and December 2014. Twelve months after initiation of treatment, 92% of patients in the first-line group (EVG: 96%, n = 22/23; DTG: 92%, n = 34/37; RAL: 90%, n = 28/31) and 88% of patients in the switch group (EVG: 94%, n = 32/34; DTG: 90%, n = 69/77; RAL: 85%, n = 67/79) showed full virological suppression (viral load <50 copies/mL). Side effects of any kind occurred in 12% (n = 12/104) of patients in the first-line group, and 10% (n = 21/219) of patients in the switch group. In the switch group neuropsychiatric side effects (depression, vertigo, and sleep disturbances) occurred more frequently in patients treated with DTG (11%, n = 10) compared to the 2 other INSTI-based cART-regimen (EVG: 2%, n = 1; RAL: 1%, n = 1). Side effects only rarely led to discontinuation of treatment (first-line-group: 2%, n = 2/104; switch-group: 1%, n = 3/219). In this real-world setting, INSTI-based ART-regimens were highly efficacious with no significant differences between any of the 3 INSTIs. Overall, side effects were only rarely observed and generally mild in all subgroups. In light of a slightly higher incidence of vertigo and sleep disturbances in patients switched to DTG, awareness of the potential onset of psychiatric symptoms is warranted during follow-up in those patients.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Quinolonas/administração & dosagem , Raltegravir Potássico/administração & dosagem , Adulto , Idoso , Antirretrovirais , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Raltegravir Potássico/efeitos adversos , Estudos Retrospectivos , Carga Viral/efeitos dos fármacos , Adulto Jovem
14.
Medicine (Baltimore) ; 98(32): e16813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393412

RESUMO

Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/µL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/µL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/µL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 &OV0556;/year vs DTG/ABC/3TC and 4164 &OV0556;/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = -548 vs DTG/ABC/3TC and ICER = -4,627&OV0556; vs EVG/cobi/FTC/TAF)The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/economia , Contagem de Linfócito CD4 , Análise Custo-Benefício , Quimioterapia Combinada , Farmacoeconomia , Honorários Farmacêuticos/estatística & dados numéricos , Feminino , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/economia , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
15.
N Engl J Med ; 381(3): 207-218, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31314965

RESUMO

BACKGROUND: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent. METHODS: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months. RESULTS: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B. CONCLUSIONS: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.).


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Administração Massiva de Medicamentos , Programas de Rastreamento , Adolescente , Adulto , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Incidência , Masculino , Prevalência , África do Sul/epidemiologia , Carga Viral , Adulto Jovem , Zâmbia/epidemiologia
16.
Medicine (Baltimore) ; 98(27): e16308, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277172

RESUMO

To discuss the prognostic correlation between hepatitis B virus DNA (HBV DNA) level and HBV-related hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).Data from HCC patients undergoing hepatectomy with pathological evidence of MVI were retrospectively collected and 1:1 propensity scoring matching (PSM) analysis was performed. According to the HBV DNA levels before and after surgery, the disease-free survival (DFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and the Cox proportional hazards regression was used to analyze the risk factors associated with the postoperative prognosis. After 1:1 PSM, 139 pairs of patients were enrolled in the high preoperative HBV DNA level group (H group) and low preoperative HBV DNA level group (L group), and after operation, patients with high preoperative HBV DNA levels were divided into the persistently high HBV DNA level group (P group) and the decreased HBV DNA level group (D group).According to the multivariate analysis, the HBV DNA level of 2000 IU/ml or greater before operation was significantly associated with the DFS (hazard ratio, 1.322; 95%CI, 1.016-1.721) and OS (hazard ratio, 1.390; 95%CI, 1.023-1.888). A persistent HBV DNA level of 2,000 IU/ml or greater after operation was also the independent risk factor of DFS (hazard ratio, 1.421; 95%CI, 1.018-1.984) and OS (hazard ratio, 1.545; 95%CI, 1.076-2.219).For the HBV-related HCC patients with MVI, preoperative high HBV DNA copies are prognostication of poorer prognosis, and effective antivirus treatment would significantly improve the patients' prognosis.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Vírus da Hepatite B , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Invasividade Neoplásica , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Carga Viral
17.
Vet Immunol Immunopathol ; 213: 109888, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307673

RESUMO

Felis catus papillomavirus type 2 (FcaPV-2) commonly infects the skin of domestic cats and has been associated with the development of skin cancer. In the present study, a FcaPV-2 virus-like particle (VLP) vaccine was produced and assessed for vaccine safety, immunogenicity, and impact on FcaPV-2 viral load. This is the first report of the use of a papillomavirus VLP vaccine in domestic cats. The FcaPV-2 VLP vaccine was given to ten adult cats that were naturally infected with FcaPV-2, and a further ten naturally infected cats were sham vaccinated as a control group. The rationale for vaccinating cats already infected with the virus was to induce neutralizing antibody titers that could prevent reinfection of new areas of skin and reduce the overall viral load, as has been demonstrated in other species. Reducing the overall FcaPV-2 viral load could reduce the risk for subsequent PV-associated cancer. The vaccine in this study was well-tolerated, as none of the cats developed any signs of local reaction or systemic illness. In the treatment group, the geometric mean anti-papillomavirus endpoint antibody titers increased significantly following vaccination from 606 (95% CI 192-1913) to 4223 (2023-8814), a 7.0-fold increase, although the individual antibody response varied depending on the level of pre-existing antibodies. Despite the immunogenicity of the vaccine, there was no significant change in FcaPV-2 viral load in the treatment group compared to the control group, over the 24 week follow-up period. A possible reason is that FcaPV-2 was already widespread in the basal skin layer of these adult cats and so preventing further cells from becoming infected had no impact on the overall viral load. Therefore, these results do not support the use of a FcaPV-2 VLP vaccine to reduce the risk for PV-associated cancer in cats in which FcaPV-2 infection is already well established. However, these results justify future studies in which the vaccine is administered to younger cats prior to FcaPV-2 infection becoming fully established.


Assuntos
Doenças do Gato/prevenção & controle , Imunogenicidade da Vacina , Infecções por Papillomavirus/veterinária , Neoplasias Cutâneas/veterinária , Carga Viral , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Doenças do Gato/virologia , Gatos , DNA Viral/sangue , Feminino , Masculino , Papillomaviridae/genética , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Reação em Cadeia da Polimerase , Testes Sorológicos , Pele/patologia , Pele/virologia , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/virologia , Vacinas de Partículas Semelhantes a Vírus/imunologia
18.
Virol J ; 16(1): 90, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319897

RESUMO

BACKGROUND: Nelson Bay orthoreovirus (NBV) was first isolated over 40 years ago from a fruit bat in Australia. Normally, NBV does not cause human diseases, but recently several NBV strains have been associated with human respiratory tract infections, thus attracting clinical attention. Autophagy, an evolutionarily conserved process in eukaryotic cells, degrades intracellular substrates, participates in multiple physiological processes, and maintains cellular homeostasis. In addition, autophagy is intimately involved in viral infection. METHODS: A new strain of NBV, isolated from a patient with a respiratory tract infection who returned to Japan from Bali, Indonesia, in 2007, was used in this study. NBV was rescued using a reverse genetics system involving cotransfection of BHK cells with 11 plasmids (pT7-L1 MB, pT7-L2 MB, pT7-L3 MB, pT7-M1 MB, pT7-M2 MB, pT7-M3 MB, pT7-S1 MB, pT7-S2 MB, pT7-S3 MB, pT7-S4 MB, and pcDNA3.1-T7), yielding NBV-MB. Recovered viruses were confirmed by immunofluorescence. The effect of NBV-MB on autophagy was evaluated by measuring the LC3-I/II proteins by immunoblot analysis after infection of BHK cells. Furthermore, after treatment with rapamycin (RAPA), 3-methyladenine (3-MA), chloroquine (CQ), or plasmid (GFP-LC3) transfection, the changes in expression of the LC3 gene and the amount of LC3-I/II protein were examined. In addition, variations in viral titer were assayed after treatment of BHK cells with drugs or after transfection with plasmids pCAGM3 and pCAGS3, which encode virus nonstructural proteins µNS and σNS, respectively. RESULTS: NBV-MB infection induced autophagy in host cells; however, the level of induction was dependent on viral replication. Induction of autophagy increased viral replication. By contrast, inhibiting autophagy suppressed NBV replication, albeit not significantly. The NBV-MB nonstructural protein µNS was involved in the induction of autophagy with viral infection. CONCLUSIONS: NBV-MB infection triggered autophagy. Also, the NBV nonstructural protein µNS may contribute to augmentation of autophagy upon viral infection.


Assuntos
Autofagia , Interações entre Hospedeiro e Microrganismos , Orthoreovirus/fisiologia , Replicação Viral , Linhagem Celular , Células HEK293 , Humanos , Infecções por Reoviridae/virologia , Genética Reversa , Carga Viral , Proteínas Virais/genética
19.
BMC Infect Dis ; 19(1): 580, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272403

RESUMO

BACKGROUND: Transcriptomic profiling has generated extensive lists of genes that respond to viral infection in mosquitoes. These gene lists contain two types of genes; (1) those that are responsible for the insect's natural antiviral defense mechanisms, including some known innate immunity genes, and (2) genes whose change in expression may occur simply as a result of infection. As genetic modification tools for mosquitoes continue to improve, the opportunities to make refractory insects via allelic replacement or delivery of small RNAs that alter gene expression are expanding. Therefore, the ability to identify which genes in transcriptional profiles may have immune function has increasing value. Arboviruses encounter a range of mosquito tissues and physiologies as they traverse from the midgut to the salivary glands. While the midgut is well-studied as the primary tissue barrier, antiviral genes expressed in the subsequent tissues of the carcass offer additional candidates for second stage intervention in the mosquito body. METHODS: Mosquito lines collected recently from field populations exhibit natural genetic variation for dengue virus susceptibility. We sought to use a modified full-sib breeding design to identify mosquito families that varied in their dengue viral load in their bodies post infection. RESULTS: By delivering virus intrathoracically, we bypassed the midgut and focused on whole body responses in order to evaluate carcass-associated refractoriness. We tested 25 candidate genes selected for their appearance in multiple published transcriptional profiles and were able to identify 12 whose expression varied with susceptibility in the genetic families. CONCLUSIONS: This method, using natural genetic variation, offers a simple means to screen and reduce candidate gene lists prior to carrying out more labor-intensive functional studies. The extracted RNA from the females across the families represents a storable resource that can be used to screen subsequent candidate genes in the future. The aspect of vector competence being assessed could be varied by focusing on different tissues or time points post infection.


Assuntos
Aedes/virologia , Vírus da Dengue/genética , Dengue/virologia , Variação Genética , Imunidade Inata/genética , Mosquitos Vetores/virologia , Animais , Vírus da Dengue/isolamento & purificação , Feminino , Perfilação da Expressão Gênica , Masculino , Carga Viral
20.
Rev Soc Bras Med Trop ; 52: e20190101, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31340370

RESUMO

INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. CONCLUSIONS: The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.


Assuntos
Linfócitos B Reguladores/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Interferon gama/imunologia , Paraparesia Espástica Tropical/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Linfócitos B Reguladores/virologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Feminino , Humanos , Masculino , Paraparesia Espástica Tropical/virologia , Linfócitos T Reguladores/virologia , Carga Viral
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