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1.
Pan Afr Med J ; 33: 218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692718

RESUMO

Introduction: Hepatitis B is a major health concern in Ghana, where prevalence of the virus remains high and most chronic patients are infected during childhood or at birth. This study aimed to determine the prevalence and main factors associated with mother-to-child transmission of hepatitis B in the context of Ghana. Methods: In this cross-sectional pilot study, we tested infants born to hepatitis B positive mothers at a hospital in the Eastern Region of Ghana to determine the prevalence of mother-to-child transmission. A questionnaire was completed by hepatitis B positive mothers to investigate the association between factors surrounding the birth of the child and whether transmission had occurred. These factors were analyzed independently using Fisher's exact test. To investigate the relationship between mother's age at the time of delivery and viral transmission, a univariate logistic regression analysis was performed. Results: The prevalence of mother-to-child transmission was 5.9%, with 51 hepatitis B positive mothers included in the study and three infants testing positive. A majority of infants received the standard hepatitis B vaccination schedule (96.1%) while two-thirds received the birth dose. There was no significant association observed between the clinical interventions reported in the study and mother-to-child transmission. No significant association was observed between the age of the mother at the time of delivery and viral transmission (OR: 1.077, 95% CI: 0.828 - 1.403, p = 0.58). Viral marker testing during pregnancy was absent in the population and could not be reliably assessed. Conclusion: There was a low prevalence of HBV mother-to-child transmission observed despite a clear absence of viral marker and viral load testing. It is recommended that viral profile analysis is performed for hepatitis B positive pregnancies to identify high risk cases.


Assuntos
Vacinas contra Hepatite B/administração & dosagem , Hepatite B/transmissão , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Complicações Infecciosas na Gravidez/virologia , Adulto , Estudos Transversais , Feminino , Gana , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Idade Materna , Projetos Piloto , Gravidez , Prevalência , Fatores de Risco , Inquéritos e Questionários , Carga Viral , Adulto Jovem
2.
Pan Afr Med J ; 33: 222, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31692792

RESUMO

Introduction: HIV-2, endemic in West Africa, has a natural resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) which makes it difficult to treat it in developing countries. Methods: We conducted a descriptive, longitudinal, prospective study over the period November 2005-June 2017. Virologic failure has been defined as any viral load greater than 50 copies/ml after 6 months of ARV treatment administered twice. Assays for detecting drug-resistance mutations was performed in the protease-coding region and in the reverse transcriptase-coding region. Results: Data from a total of 110 patients were collected. The patients had a median age of 46 years (ranging from 18 to 67) with a sex-ratio F/M of 2.54. At inclusion, viral load could be assessed in 44% of cases with a median of 935cp/ml (ranging from 17 to 144038). Antiretroviral regimen consisted of a combination of 2 NRTIs and 1IP in 94% of cases. The median follow-up was 1200 days (ranging from 1 to 3840); 94 then 76 patients completed their 12-month and 24-month assessments respectively. At 24-month follow-up, 39 patients had virologic failure, reflecting a prevalence of 39% estimated at 33% at 12-month follow-up and at 11% at 24-month follow-up; NRTIs resistance was observed in 45% of patients, IP resistance in 41% of patients while multi-NRTIs resistance and multi-IP resistance in 30% of patients. Conclusion: Currently, there is an urgent need to make available the new therapeutic classes of ARV for second line ART for patients living with HIV-2 with therapeutic failure in resource-limited settings.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , HIV-2/isolamento & purificação , Inibidores da Transcriptase Reversa/administração & dosagem , Adolescente , Adulto , Idoso , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-2/efeitos dos fármacos , HIV-2/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Transcriptase Reversa/farmacologia , Senegal/epidemiologia , Carga Viral , Adulto Jovem
3.
Klin Lab Diagn ; 64(10): 635-640, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31742959

RESUMO

To analyze the method for detecting HBV DNA in peripheral blood at low viral load and evaluate its significance in identifying HBsAg-negative viral hepatitis B. In this work, samples of blood and liver tissue biopsy material were used from 128 patients living in the Russian Federation and the Republic of Uzbekistan without CHB and with CHB confirmed detection of circle covalently closed HBV DNA in hepatocytes. Plasma viral load was measured using the «AmpliSens® HBV-Monitor-FL¼ kit. HBV at low viral load was detected by nested PCR. Analytical sensitivity was checked by step dilution. According to our method, at the first stage, an asymmetric PCR is carried out using extended oligonucleotide primers with different melting points, complementary to the hepatitis B different genotypes genomes greatest similarity region. To increase the sensitivity, a second PCR is performed using the first reaction amplification product and internal primers. The sensitivity of the method for DNA extraction from 100 µl of plasma was 5 IU / ml, specificity 100%. Since, in spite of the HBV genotypes characteristic geographical distribution, the detection of "alien" genovariants for certain territories is becoming more frequent, we tested the method in geographically remote but active international relations with the Russian Federation regions with a high frequency of hepatotropic viruses. The developed method for detecting HBV DNA in blood plasma at low viral load based on PCR technology allows the various HBV gene variants identification and genotyping, both characteristic and rare in the Russian Federation, circulating in other world regions. The method can be used to detect HBV in risk groups, in a population, as well as when screening blood donors in order to ensure the blood transfusions safety.


Assuntos
DNA Viral/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Antígenos de Superfície da Hepatite B , Humanos , Reação em Cadeia da Polimerase , Federação Russa , Carga Viral
4.
Arch Virol ; 164(12): 3019-3026, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31598843

RESUMO

Polyethyleneimine (PEI) is a chemical compound that used is as a carrier in gene therapy/delivery. Some studies have investigated the microbicidal potential and antiviral activity (prophylactic or therapeutic) of PEI and its derivatives. The aim of this study was to investigate the effect of branched polyethyleneimine (bPEI) on human immunodeficiency virus (HIV) replication. Infected cells were treated with bPEI for 36 hours, and the concentration of the viral protein P24 (as a virus replication marker) was determined in cell culture supernatants. This study indicated that bPEI increased HIV replication and decreased the viability of infected cells through cytotoxicity. The toxicity of bPEI its association with and cell death (apoptosis, autophagy and necrosis) have been reported in several studies. To investigate bPEI-induced cytotoxicity, we examined apoptosis and autophagy in cells treated with bPEI, and a significant increase in HIV viral load, the P24 antigen level, autophagy, and necrosis observed. Thus, treatment with bPEI leads to cytotoxicity and higher HIV virus yield.


Assuntos
Infecções por HIV/virologia , HIV/efeitos dos fármacos , Polietilenoimina/farmacologia , Replicação Viral/efeitos dos fármacos , Autofagia/efeitos dos fármacos , HIV/genética , HIV/fisiologia , Proteína do Núcleo p24 do HIV/genética , Proteína do Núcleo p24 do HIV/metabolismo , Infecções por HIV/fisiopatologia , Humanos , Polietilenoimina/química , Carga Viral/efeitos dos fármacos
5.
Gynecol Oncol ; 155(2): 245-253, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604665

RESUMO

OBJECTIVE: We assessed whether human papillomavirus (HPV) viral load is an independent predictor of underlying cervical disease and its diagnostic accuracy by age. METHODS: The Biomarkers of Cervical Cancer Risk study was a case-control study from 2001 to 2010 in Montréal, Canada. Cases were histologically-confirmed cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), or cervical cancer cases. Controls were women presenting for routine screening with normal cytology results. We quantified HPV16/18/31/33/45 viral load from exfoliated cervical cells using a real-time PCR assay. Diagnostic accuracy of viral load was assessed using the area under the receiver operating characteristic curve (AUC). We restricted the analysis to the 632 cases and controls who were HPV16/18/31/33/45 positive. RESULTS: Geometric mean HPV16/18/31/33/45 viral load increased with severity of lesion grade, ranging from 0.7, 3.1, 4.8, 7.2, and 12.4 copies/cell in normal, CIN1, CIN2, CIN3&AIS, and cervical cancer respectively. The adjusted odds ratio of CIN1+ and CIN2+ increased respectively by 1.3 (95%CI 1.1-1.4) and 1.2 (95%CI 1.1-1.3) per log-transformed viral copy/cell increase of HPV16/18/31/33/45. This association was mainly driven by HPV16, 18, and 31 viral loads. The AUC of HPV16/18/31/33/45 viral load for discriminating between normal and CIN1+ women was 0.70 (95%CI 0.64-0.76) in HPV-positive women, and was 0.76 (95%CI 0.66-0.86) for women ≥30 years and 0.66 (95%CI 0.58-0.74) for women under 30 years. CONCLUSIONS: HPV viral load has lower diagnostic accuracy than has been reported for other HPV screening triage tests. However, it may be useful for triaging HPV tests in settings without cytology results such as HPV self-sampling.


Assuntos
Adenocarcinoma in Situ/virologia , Alphapapillomavirus/isolamento & purificação , Neoplasia Intraepitelial Cervical/virologia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Quebeque , Carga Viral/fisiologia , Adulto Jovem
6.
BMC Infect Dis ; 19(1): 839, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606032

RESUMO

BACKGROUND: Household contact tracing of index TB cases has been advocated as a key part of TB control for many years, but has not been widely implemented in many low-resource setting because of the current dearth of high quality evidence for effectiveness. Innovative strategies for earlier, more effective treatment are particularly important in contexts with hyper-endemic levels of HIV, where levels of TB infection remain extremely high. METHODS: We present the design of a household cluster-randomised controlled trial of interventions aimed at improving TB-free survival and reducing childhood prevalence of Mycobacterium tuberculosis infection among household contacts of index TB cases diagnosed in two provinces of South Africa. Households of index TB cases will be randomly allocated in a 1:1 ratio to receive either an intensified home screening and linkage for TB and HIV intervention, or enhanced standard of care. The primary outcome will compare between groups the TB-free survival of household contacts over 15 months. All participants, or their next-of-kin, will provide written informed consent to participate. DISCUSSION: Evidence from randomised trials is required to identify cost-effective approaches to TB case-finding that can be applied at scale in sub-Saharan Africa. TRIAL REGISTRATION: ISRCTN16006202 (01/02/2017: retrospectively registered) and NHREC4399 (11/04/2016: prospectively registered). Protocol version: 4.0 (date: 18th January 2018).


Assuntos
Busca de Comunicante/métodos , Tuberculose/prevenção & controle , Adulto , Criança , Análise Custo-Benefício , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Estudos Retrospectivos , Risco , África do Sul/epidemiologia , Padrão de Cuidado , Resultado do Tratamento , Teste Tuberculínico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Carga Viral
7.
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
8.
Medicine (Baltimore) ; 98(42): e17571, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626125

RESUMO

RATIONALE: Severe fever with thrombocytopenia syndrome (SFTS) is a recently recognized fatal infectious disease caused by the SFTS virus, and severe cases are complicated by the presence of hemophagocytic lymphohistiocytosis (HLH) associated with a cytokine storm. Herein, we report on serial changes of serum cytokine levels and viral load in a severe case of SFTS. PATIENT CONCERNS: A 63-year-old Japanese woman presented with high-grade fever, abdominal pain, diarrhea, impaired consciousness, leukocytopenia, and thrombocytopenia. DIAGNOSIS: SFTS was diagnosed based on a positive serum test for SFTS virus RNA and electroencephalogram (EEG) findings of encephalopathy. INTERVENTIONS: The patient was treated with supportive therapy, including steroid pulse therapy (intravenous methylprednisolone 1 g/d for 3 days) for HLH and intravenous recombinant thrombomodulin 19200 U/d for 7 days for disseminated intravascular coagulation. OUTCOMES: Treatment for 7 days improved both symptoms and abnormal EEG findings, and SFTS virus RNA disappeared from the serum at day 10 from the onset of symptoms. The serum cytokines and chemokines analysis during the clinical course revealed 2 distinct phases: the acute phase and the recovery phase. The cytokines and chemokines elevated in the acute phase included interleukin (IL)-6, IL-10, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, interferon-γ-induced protein-10, and fractalkine, while the IL-1ß, IL-12p40, IL-17, and vascular endothelial growth factor levels were higher in the recovery phase. CONCLUSION: These observations suggest that the cytokines and chemokines elevated in the acute phase may reflect the disease severity resulted in a cytokine storm, while those in the recovery phase may be attributed to T-cell activation and differentiation.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Febre/sangue , Febre por Flebótomos/sangue , Phlebovirus/fisiologia , Trombocitopenia/sangue , Carga Viral , Biomarcadores/sangue , Feminino , Febre/virologia , Humanos , Pessoa de Meia-Idade , Febre por Flebótomos/virologia , Índice de Gravidade de Doença , Síndrome , Trombocitopenia/virologia
9.
Medicine (Baltimore) ; 98(42): e17590, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626130

RESUMO

To date, a small number of studies concerning the effects and safety of tenofovir disoproxil fumarate (TDF) in Chinese individuals were conducted. In this study, we aimed to assess the antiviral effects and nephrotoxicity of TDF in Chinese patients with chronic hepatitis B virus (HBV) infection.Patients with chronic HBV infection were prospectively recruited and TDF treatment was given for 96 weeks. HBV serologic markers, HBV DNA, creatinine and phosphorus were collected.Fifty-seven treatment-naïve and 48 treatment-experienced patients were recruited. Irrespective of the prior treatment history, more than 95% of patients achieved virological response during 96 weeks treatment with TDF. Estimated glomerular filtration rate (eGFR) significantly declined in the first year of treatment in patients with chronic hepatitis B or younger age (<65 years old) (both P < .05), while that was not achieved in patients with liver cirrhosis or older age (≥65 years old) (both P > .05). For patients who were treatment-naïve or treated previously with adefovir dipivoxil, eGFR declined at the 48th week; however, eGFR was partially recovered at the 96th week. Furthermore, multivariable analysis showed that basal eGFR <90 mL/min/1.73 m (P = .001; odds ratio: 4.821; 95% confidence interval: 1.904-12.206) is the only independent risk factor for eGFR <90 mL/min/1.73 m at the 96th week.TDF has potent antiviral effect in both treatment-naïve and treatment-experienced patients.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Carga Viral , Adulto , Antivirais/uso terapêutico , China/epidemiologia , DNA Viral/análise , Feminino , Seguimentos , Antígenos E da Hepatite B/análise , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
10.
Afr Health Sci ; 19(2): 1988-1992, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31656481

RESUMO

Background: Previous trials have investigated the effect of hepatitis C on lung functions; however, the role of viral load levels is unclear. The aim of this study was to investigate the effect of HCV viremia status on lung functions. Methods: This study was in 60 patients with chronic hepatitis C (CHC). Patients were classified into three groups (non-viremic, low-viremic and high-viremic) based on serum HCV RNA levels. Spirometric parameters (FEV1, FVC, FEV1/FVC) and the proportion of patients with spirometric abnormalities were compared between three groups. Results: High-viremic and low-viremic patients showed a significantly higher prevalance of spirometric abnormality than observed in non-viremic patients (p=0.02). Moreover, there was a significant moderate correlation between viremia level and the percentage of spirometric abnormalities (Cramer's U value=0.452, p=0.002). High-viremic patients were 14.2 times more likely to exhibiting pulmonary dysfunction than non-viremic patients. Additionally, spirometric parameters FEV1 and FVC were significantly reduced in high-viremic and low-viremic patients compared to those in non-viremic patients (p=0.013 and p<0.001 respectively). Conclusion: These results indicate that persistent HCV infection may be associated with reduced pulmonary functions, especially in patients with high viremia levels. Therefore, these patients should be carefully monitored for lung function.


Assuntos
Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/análise , Hepatite C Crônica/diagnóstico , Pulmão/fisiologia , RNA Viral/sangue , Viremia/diagnóstico , Adulto , Feminino , Hepatite C Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Testes de Função Respiratória , Espirometria , Carga Viral , Viremia/epidemiologia , Viremia/virologia
11.
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
12.
Arch Virol ; 164(12): 2919-2930, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520220

RESUMO

Human bocavirus (HBoV) has been detected primarily in children with acute lower respiratory tract disease (LRTD), but its occurrence, clinical profile, and role as a causative agent of RTD are not clear. The aim of this study was to investigate the prevalence and the potential clinical relevance of HBoV. Using molecular tests, we tested 1352 nasopharyngeal samples obtained between October 1, 2017 and April 30, 2018 from children up to the age of 16 with RTD for the presence of HBoV DNA and 20 other respiratory pathogens at three different hospitals in Belgium. HBoV was detected in 77 children with a median age of 10.6 months. Consecutive samples were available for 15 HBoV-positive children and showed persistent HBoV positivity in four of them. Monoinfection was observed in six infants. Four of them were born prematurely and were infected during hospitalization at the neonatal intensive care unit (NICU). Only one of these six monoinfected children was diagnosed with recurrent wheezing due to HBoV. This child was carried to term and had a high viral load. Coinfections, most frequently with rhinovirus (52.1%) and adenovirus (49.3%), were observed in 72 patients. In seventeen of them in which HBoV was present at high viral load or higher viral load than its copathogens, bronchi(oli)tis (n = 8), recurrent wheezing (n = 8) or episodic wheezing (n = 1) were diagnosed. Our results suggest that HBoV infection at high viral load in infants is associated with wheezing (P = 0.013, Cramer's V = 0.613).


Assuntos
Bocavirus Humano/isolamento & purificação , Infecções por Parvoviridae/diagnóstico , Infecções Respiratórias/virologia , Adolescente , Bélgica/epidemiologia , Criança , Pré-Escolar , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , DNA Viral/genética , Feminino , Bocavirus Humano/genética , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Nasofaringe/virologia , Infecções por Parvoviridae/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/virologia , Prevalência , Estudos Retrospectivos , Carga Viral
13.
AIDS Behav ; 23(Suppl 3): 287-295, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31520241

RESUMO

Test and Rapid Response Treatment (TRRT) linkage programs have demonstrated improved HIV suppression rates. This paper describes the design and implementation of the Miami TRRT initiative and its clinical impact. Assisted by a dedicated care navigator, patients receiving a reactive HIV rapid test at the Florida Department of Health STD Clinic were offered same-day HIV care at the University of Miami/Jackson Memorial Medical Center Adult HIV Outpatient Clinic. Patient retention and labs were tracked for 12 months. Of the 2337 individuals tested, 46 had a reactive HIV test; 41 (89%) consented to participate. For the 36 patients in continued care for a year, 33 (91.7%) achieved virological suppression (< 200 copies/mL) within 70 days of their reactive HIV rapid test; at 12 months, 35 (97.2%) remained suppressed, and mean CD4 T cell counts increased from 452 ± 266 to 597 ± 322 cells/mm3. The Miami TRRT initiative demonstrated that immediate linkage to care is feasible and improves retention and suppression in a public/academic medical center in the U.S. South.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Programas de Rastreamento/métodos , Navegação de Pacientes , Cooperação e Adesão ao Tratamento/psicologia , Centros Médicos Acadêmicos , Adulto , Instituições de Assistência Ambulatorial , Contagem de Linfócito CD4 , Continuidade da Assistência ao Paciente , Feminino , Florida , Infecções por HIV/virologia , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Resultado do Tratamento , Carga Viral
14.
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
16.
BMC Infect Dis ; 19(1): 815, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533639

RESUMO

BACKGROUND: Elite controllers (EC), a small subset of the HIV-positive population (< 1%), suppress HIV viremia below the limit of quantification of clinical viral load assays in the absence of antiretroviral therapy (ART). However, there is a paucity of longitudinal data detailing the viral and immune dynamics or HIV reservoir seeding during acute infection in individuals that go on to become Elite Controllers. CASE PRESENTATION: In this report, we describe a case of a 42 year old woman diagnosed during acute infection who rapidly and permanently suppressed her viremia in the absence of antiretroviral therapy (ART). Rapid antibody/antigen testing was either negative or equivocal during acute infection, despite subsequent viral load testing at that time point with 71,550 plasma HIV RNA copies/mL, making initial diagnosis challenging. The patient subsequently developed detectable anti-HIV antibodies and an increase in HIV-specific CD8+ T cell responses to overlapping subtype C HIV gag peptide; very low-level plasma viremia (0.84 RNA copies/mL) was detected by an ultrasensitive assay 2 years following infection. Subsequently, she was started on ART for multifocal furunculosis despite continued suppression of virus and stable CD4+ T cell counts. Following ART initiation, HIV specific antibody levels and CD8+ T cell responses increased, but no HIV DNA or RNA was able to be isolated from large numbers of peripheral blood CD4+ T cells. CONCLUSION: This case provides important information regarding the establishment of elite HIV control during acute infection and also demonstrates an increase in HIV-specific immune responses following ART despite undetectable peripheral blood cellular measures of HIV persistence. This case also highlights the challenges in diagnosing acute HIV infection without the use of viral load testing in this rare elite controller phenotype.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/patologia , HIV-1/genética , Humanos , RNA Viral/sangue , Carga Viral
17.
BMC Infect Dis ; 19(1): 820, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533648

RESUMO

BACKGROUND: The aim of this study was to establish the prevalence of lipodystrophy and its association to cumulative exposure to antiretroviral drugs. METHOD: We conducted a cross sectional study in all HIV- infected patients attending the HIV clinic in the Centre hospitalier universitaire de Montréal (CHUM) with DEXA scan. Lipodystrophy was defined as a trunk/limb fat ratio ≥ 1.5. Association between cumulative exposure to antiretroviral (measured in years of use) with trunk/limb fat ratio (coded as a continuous variable) was assessed using univariate and multivariate linear regression for each antiretroviral drug with at least 40 exposed patients. RESULTS: One hundred sixty-six patients were included. Seventy-five percent were male, median age was 56 years, 67% were Caucasian. Overall, prevalence of lipodystrophy was 47%, with a mean trunk/limb fat ratio of 1.87, SD = 1.03, min = 0.6 and max = 5.87. Each 10-year increase in age and HIV infection duration was associated with an average increase of 0.24 and 0.34 for the trunk/limb fat ratio respectively. (p = 0.003, p = 0.002, respectively) Patients classified as lipodystrophic were more likely to be diabetic (50 vs. 28%, p = 0.07) and to have dyslipidemia (47 vs. 19%, p = 0.01). According to viral load at DEXA test, each one log increase was associated with less probability (0.7) of lipodystrophy. (p = 0.01) Among ARV drugs tested, there was an association between years of use of d4T, ritonavir and raltegravir and higher trunk/limb fat ratio (indicating more lipodystrophy) (p < 0.05). CONCLUSION: Lipodystrophy is very common in HIV infected patients and is correlated with duration of some new antiretroviral drugs.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Síndrome de Lipodistrofia Associada ao HIV/diagnóstico , Absorciometria de Fóton , Adulto , Idoso , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/etiologia , Feminino , Síndrome de Lipodistrofia Associada ao HIV/epidemiologia , Síndrome de Lipodistrofia Associada ao HIV/etiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Carga Viral
18.
Int J Infect Dis ; 86: 178-187, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398453

RESUMO

OBJECTIVES: Most previous studies on poor immunological responders (PIRs) have been performed on one cohort at one time-point following highly active antiretroviral therapy (HAART). The aim of this study was to investigate whether there are different subtypes of PIR and whether a certain population might achieve better immune reconstitution following longer HAART. METHODS: This study was designed as an ambispective cohort study, including a 4-5-year retrospective study and a 2-year prospective follow-up investigation. Thymic output, activated T cell and regulatory T cell (Treg) subset frequencies, expression levels of interferon-stimulated genes, and plasma concentrations of neopterin were determined at 4-5 years and 6-7 years following HAART initiation. RESULTS: PIRs were subdivided into two populations after 4-5 years of HAART, according to the kinetics of T cell recovery. Type II PIRs exhibited a significantly lower percentage of naïve CD4+ T cells and CD31+ naïve CD4+ T cells compared with type I PIRs. After an additional 2 years of HAART treatment, type I PIRs showed a better outcome than type II PIRs. Furthermore, it was found that 2 years of additional HAART could persistently improve thymic output. CONCLUSIONS: The two PIR subgroups are different in terms of immune characteristics and the response to prolonged HAART.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Esquema de Medicação , Feminino , Seguimentos , HIV-1/imunologia , Humanos , Ativação Linfocitária , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Linfócitos T Reguladores/imunologia , Carga Viral
19.
Transplant Proc ; 51(6): 1801-1809, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399166

RESUMO

BK viremia (BKV) is a recognized and potentially serious problem in renal transplantation. The risk factors and the impact of BKV on renal allograft and patient survival are controversial. This study reports an 8-year, single-center experience on the prevalence, risk factors, and outcomes of BKV in kidney transplant recipients. This is a retrospective analysis of all patients who received a kidney transplant at the University of Kentucky and had BK viral titers available from 2009 to 2017. BKV was defined by a polymerase chain reaction viral load of ≥ 10,000 copies per mL. Demographic, clinical, and laboratory data generated during routine outpatient follow up and inpatients records were collected. Independent risk factors for BKV were determined using uni- and multivariate analysis. Graft and patient survival was compared using Kaplan-Meier analysis, and the severity of polyomavirus nephropathy on biopsy was scored using the Banff 2017 classification. We identified 122 BK positive (19%) and 527 BK negative (81%) patients. BKV developed after a median of 115 days (range, 80-249 days) following kidney transplantation. The 1-, 5-, and 10-year graft survival was 97%, 75%, and 33% in the BKV group and 96%, 85%, and 71% in the BK negative group, respectively. Likewise, the 1-, 5-, and 10-year patient survival was 98%, 84%, and 52% in the BKV group and 98%, 92%, and 84% in the BK negative group. Male sex, age at transplantation, maintenance steroids, and alemtuzumab induction were associated with developing BKV in the multivariate analysis. We concluded that BKV is not uncommon after renal transplantation. The determinants for BKV are male sex, older transplant recipients, and maintenance steroids. BKV adversely affected graft and patient survival. A unified approach for BKV and polyomavirus nephropathy treatment is needed.


Assuntos
Vírus BK , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/virologia , Complicações Pós-Operatórias/virologia , Infecções Tumorais por Vírus/virologia , Viremia/virologia , Adulto , Biópsia , Feminino , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Rim/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Carga Viral
20.
Transplant Proc ; 51(7): 2482-2485, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31405736

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a global health problem, and the need for liver transplants is ever-growing. For optimal surgical success, risk factors must be identified and HCV viral load must be reduced to a minimum to avoid complications. In this study, we aimed to investigate the role of HCV viral load on the post-transplant biliary complications. METHOD: Between 2004 and 2018, the cases of 114 liver transplant recipients with HCV infection were retrospectively reviewed. Data collection included demographic variables, preoperative and postoperative amount of serum HCV RNA copies, preoperative diagnosis of hepatocellular carcinoma (HCC), and postoperative biliary complications in the early and late period. After missing values were excluded, the remaining 97 patients were divided into 2 groups according to preoperative HCV RNA status (Group A: HCV RNA [+] and Group B: HCV RNA [-]). RESULTS: Demographic parameters were similar among both groups. There were 67 patients in Group A and 30 patients in Group B. The overall rate of biliary complications was higher in Group A without statistical significance (20% [n = 14] vs 13% [n = 4], respectively, P = .573). Biliary stricture occurrence in the late period was also higher in Group A. In HCC (+) patients (n = 26), biliary complications were significantly higher compared to HCC (-) patients (34% vs 12%, P = .018). However, in patients with biliary complications, the rate of multiple duct anastomoses was higher with no statistical significance (45% vs 26%, respectively, P = .14). CONCLUSION: The biliary complications on patient survival has been previously established, and this is mostly evident in those patients with viral etiology and hepatocellular carcinoma. As was also suggested in our study, hepatocellular carcinoma and positive viral status should be considered as predisposing factors for postoperative biliary complications after liver transplantation. However, the rate of multiple duct anastomoses should also be taken into consideration. New standards of antiviral medications and bridge therapy for HCC may improve transplant outcomes.


Assuntos
Carcinoma Hepatocelular/complicações , Hepatite C Crônica/virologia , Neoplasias Hepáticas/complicações , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus , Hepatite C Crônica/complicações , Humanos , Incidência , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Carga Viral
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