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3.
Viruses ; 13(2)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498165

RESUMO

Anal squamous cell carcinoma is the most frequent virus-related non-AIDS-defining neoplasia among HIV-infected individuals, especially MSM. The objectives of this study were to analyze the effectiveness of the quadrivalent HPV (qHPV) vaccine to prevent anal ≥ high-grade squamous intraepithelial lesions (≥HSILs), external ano-genital lesions (EAGLs), and infection by qHPV vaccine genotypes in HIV+ MSM, and to study the immunogenicity of the vaccine and risk factors for ≥ HSILs. This study is nested within a randomized, double-blind, placebo-controlled trial of the qHPV vaccine, which enrolled participants between May 2012 and May 2014, with a 48-month follow-up. A vaccine or placebo was administered at 0, 2, and 6 months, and vaccine antibody titers were evaluated at 7, 12, 24, 36, and 48 months. Data were gathered at 12, 24, 36, and 48 months on sexual habits, CD4/CD8 cell/counts, HIV viral load, and the results of cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope). The study included 129 patients (mean age of 38.8 years, 40 [31%] with a history of AIDS, 119 [92.2%] receiving ART, and 4 [3.3%] with virological failure), 66 (51.2%) in vaccine arm and 63 (48.4%) in placebo arm. The vaccine and placebo groups did not differ in ≥ HSILs (14.1 vs. 13.1%, respectively, p = 0.98) or EAGL (11.1 vs. 6.8%, p = 0.4) rates during follow-up; however, a protective effect against HPV 6 was observed during the first year of follow-up in the vaccine versus placebo group (7.5% vs. 23.4%; p = 0.047). A between-arm difference (p = 0.0001) in antibodies against qHPV vaccine genotypes was observed at 7 months (76.9% in vaccine arm vs. 30.2% in placebo arm), 12 months (68.1% vs. 26.5%), 24 months (75% vs. 32.5%), 36 months (90% vs. 24.4%), and 48 months (87.2% vs. 30%). Finally, the factor associated with the risk of anal ≥ HSIL onset during the four-year follow-up was the receipt of the last dose of the vaccine less than 6 months earlier in comparison to those vaccinated for a longer period (82.4% vs. 17.6% (OR 0.869 [95% CI, 0.825-0.917]). Vaccine and placebo arms did not significantly differ in ≥ HSIL or EAGL rates or in protection against infection by HPV genotype vaccine except for HPV6 at 12 months after the first dose. A long-lasting immune response was observed in almost all the vaccinated men. The main protective factor against ≥ HSIL was to have completed the vaccination regimen more than 6 months earlier.


Assuntos
Anticorpos Antivirais/sangue , Neoplasias do Ânus/prevenção & controle , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Adulto , Canal Anal/virologia , Neoplasias do Ânus/virologia , Contagem de Linfócito CD4 , Coinfecção/virologia , Infecções por HIV/virologia , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Análise de Regressão , Minorias Sexuais e de Gênero , Espanha , Carga Viral/imunologia
4.
Sci Rep ; 10(1): 21417, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293554

RESUMO

SARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients. We evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 h after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors. We included 219 patients (mean age of 63.6 ± 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404-433), and after treatment QTc was prolonged to 423 ms (405-438) (P < 0.001), with an average increase of 1.8%. Most of the patients presented a normal QTc under treatment, with only 31 cases (14.1%) showing a QTc interval > 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation. Ambulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.


Assuntos
Antivirais/efeitos adversos , Azitromicina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Inibidores de Proteases/efeitos adversos , Fibrilação Ventricular/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Estado Terminal , Quimioterapia Combinada , Eletrocardiografia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Inibidores de Proteases/uso terapêutico , Fatores de Risco , SARS-CoV-2/efeitos dos fármacos , Adulto Jovem , Tratamento Farmacológico da COVID-19
5.
Medicine (Baltimore) ; 96(39): e8109, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953633

RESUMO

Squamous cell carcinoma of anus (SCCA) is one of the most frequent non-AIDS-defining diseases in HIV patients, mainly in men who have sex with men (MSM), and it is associated with human papillomavirus (HPV) infection.To determine the prevalence of high-risk HPV (HR-HPV) genotypes, premalignant lesions (HSIL) and SCCA in a cohort of HIV-positive MSM; to study the distribution of HPV genotypes according to anal histology results; and to analyze risk factors for this infection.This prospective single-center study was conducted between May 2010 and September 2016. At the study visit, cotton swabs were used to collect anal samples for cytology study in ThinPrep Pap Test liquid medium (Thin Prep Processor 2000, Hologic Corp, USA), and for HPV PCR (Linear Array HPV Genotyping Test). After, high-resolution anoscopy (HRA) (Zeiss 150 fc) was carried out. Logistic regression analysis was performed to identify risk factors for HR-HPV infection.The study included 319 patients, with mean age of 36.7 years; HR-HPV was detected in 81.3%. The prevalence of HSIL was 13.5% and SCCA was 0.3%. With regard to the distribution of HPV genotypes according to histology results, HPV 16 was the most frequent genotype in normal anal mucosa (26.7%), in LSILs (36.9%), and in HSILs (38%). In multivariate analysis, CD4 nadir < 200 cells/µL was the factor associated with infection by HR-HPV (OR 3.66, 95% CI 1.05%-12.75%).HIV-positive MSM showed a high prevalence of HSIL+ lesions and of infection by oncogenic HPV, which appears to be favored by a deficient immune system. HPV 16 was the most frequently isolated genotype in anal mucosa, regardless of lesion type.


Assuntos
Neoplasias do Ânus/virologia , Carcinoma de Células Escamosas/virologia , Infecções por HIV/complicações , Homossexualidade Masculina , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Adulto , Canal Anal/virologia , Antirretrovirais/uso terapêutico , Neoplasias do Ânus/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Endoscopia Gastrointestinal/métodos , Genótipo , Infecções por HIV/virologia , Papillomavirus Humano 16/genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Oncogenes , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/virologia , Prevalência , Estudos Prospectivos , Fatores de Risco
6.
AIDS Res Ther ; 14(1): 34, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28720147

RESUMO

BACKGROUND: Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine were evaluated in HIV-positive Spanish MSM. The prevalence of High Squamous Intraepithelial Lesions (HSIL) and genotypes of high-risk human papillomavirus (HR-HPV) were also determined, as well as risk factors associated with the presence of HR-HPV in anal mucosa. METHODS: This is a randomised, double blind, placebo-controlled trial of the quadrivalent HPV (qHPV) vaccine. The study enrolled from May 2012 to May 2014. Vaccine and placebo were administered at 0, 2 and 6 months (V1, V2, V3 clinical visits). Vaccine antibody titres were evaluated at 7 months. Cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope) were performed at V1. RESULTS: Patients (n = 162; mean age 37.9 years) were screened for inclusion; 14.2% had HSIL, 73.1% HR-HPV and 4.5% simultaneous infection with HPV16 and 18. Study participants (n = 129) were randomized to qHPV vaccine or placebo. The most common adverse event was injection-site pain predominating in the placebo group [the first dose (83.6% vs. 56.1%; p = 0.0001]; the second dose (87.8% vs. 98.4%; p = 0.0001); the third dose (67.7% vs. 91.9%; p = 0.0001). The vaccine did not influence either the viral load of HIV or the levels of CD4. Of those vaccinated, 76% had antibodies to HPV vs. 30.2% of those receiving placebo (p = 0.0001). In the multivariate analysis, Older age was associated with lower HR-HPV infection (RR 0.97; 95% CI 0.96-0.99), and risk factor were viral load of HIV >200 copies/µL (RR 1.42 95% CI 1.17-1.73) and early commencement of sexual activity (RR 1.35; 95% CI 1.001-1.811). CONCLUSIONS: This trial showed significantly higher anti-HR-HPV antibody titres in vaccinated individuals than in unvaccinated controls. There were no serious adverse events attributable to the vaccine. In our cohort, 1 of every 7 patients had HSIL and the prevalence of combined infection by genotypes 16 and 18 was low. This suggests that patients could benefit from receiving qHPV vaccine. Older age was the main protective factor against HR-HPV infection, and non-suppressed HIV viremia was a risk factor. CLINICAL TRIAL REGISTRATION: ISRCTN14732216 ( http://www.isrctn.com/ISRCTN14732216 ).


Assuntos
Anticorpos Antivirais/sangue , Neoplasias do Ânus/prevenção & controle , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/efeitos adversos , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Adulto , Canal Anal/virologia , Neoplasias do Ânus/virologia , Contagem de Linfócito CD4 , Coinfecção/virologia , Método Duplo-Cego , Infecções por HIV/virologia , Homossexualidade Masculina , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/uso terapêutico , Humanos , Masculino , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Placebos/uso terapêutico , Espanha , Carga Viral/imunologia , Viremia/virologia
7.
Rev. chil. infectol ; Rev. chil. infectol;32(6): 706-709, ilus
Artigo em Espanhol | LILACS | ID: lil-773278

RESUMO

Intravesical therapy with live-attenuated Mycobacterium bovis strain have demonstrated to be effective in the treatment of recurrent and high-grade superficial bladder tumors. The use of this therapy is widely extended; however spreading of bacillus from the injection site could be one rare complication that may cause infection in different locations. An appropriate anamnesis is very important to establish an etiological diagnostic of possible infections caused by M. bovis BCG. Laboratory diagnosis at species level is difficult because of the high genetic similarity (99.9%) with the other member of Mycobacterium tuberculosis complex. We present a case report who developed tuberculous spondylodiscitis by M. bovis BCG, which had a history of intravesical instillation for treatment of bladder cancer.


Las instilaciones intravesicales con la cepa viva atenuada de Mycobacterium bovis han demostrado su eficacia en el tratamiento de cáncer urotelial de vejiga. Su uso está ampliamente difundido; sin embargo, una reacción adversa infrecuente es la extravasación del bacilo del lugar de acción pudiendo causar infecciones en otras localizaciones. Una correcta anamnesis del paciente ayuda a orientar la etiología de posibles infecciones relacionadas con éste microorganismo. El diagnóstico de laboratorio a nivel de especie es dificultoso ya que comparte un 99,9% de identidad genética con los otros miembros del complejo Mycobacterium tuberculosis. Se presenta el caso de un paciente que desarrolló una espondilodiscitis tuberculosa por M. bovis BCG, el cual tenía antecedentes de instilaciones intravesicales para el tratamiento del cáncer de vejiga.


Assuntos
Idoso , Humanos , Masculino , Abscesso/microbiologia , Discite/microbiologia , Mycobacterium bovis , Doenças da Medula Espinal/microbiologia , Abscesso/diagnóstico , Discite/diagnóstico , Imageamento por Ressonância Magnética , Doenças da Medula Espinal/diagnóstico
9.
PLoS One ; 10(4): e0123590, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25849412

RESUMO

OBJECTIVES: To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). METHODS: This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. RESULTS: Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). CONCLUSIONS: When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV suppression with treatment protects against the appearance of HSIL [corrected].


Assuntos
Canal Anal/patologia , Neoplasias do Ânus/diagnóstico , Infecções por HIV/complicações , Homossexualidade Masculina , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase/métodos , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Adulto , Canal Anal/virologia , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/virologia , Estudos Transversais , Citodiagnóstico , DNA Viral/genética , Feminino , Infecções por HIV/epidemiologia , Soropositividade para HIV , Humanos , Masculino , Mucosa/patologia , Mucosa/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Espanha/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/virologia
10.
Rev Chilena Infectol ; 32(6): 706-9, 2015 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-26928510

RESUMO

Intravesical therapy with live-attenuated Mycobacterium bovis strain have demonstrated to be effective in the treatment of recurrent and high-grade superficial bladder tumors. The use of this therapy is widely extended; however spreading of bacillus from the injection site could be one rare complication that may cause infection in different locations. An appropriate anamnesis is very important to establish an etiological diagnostic of possible infections caused by M. bovis BCG. Laboratory diagnosis at species level is difficult because of the high genetic similarity (99.9%) with the other member of Mycobacterium tuberculosis complex. We present a case report who developed tuberculous spondylodiscitis by M. bovis BCG, which had a history of intravesical instillation for treatment of bladder cancer.


Assuntos
Abscesso/microbiologia , Discite/microbiologia , Mycobacterium bovis , Doenças da Medula Espinal/microbiologia , Abscesso/diagnóstico , Idoso , Discite/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças da Medula Espinal/diagnóstico
11.
PLoS One ; 9(3): e92376, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24676139

RESUMO

OBJECTIVES: Chronic infection with oncogenic HPV genotype is associated with the development of anal dysplasia. Antiretroviral therapy (ART) has been shown to decrease the incidence of cervical carcinoma in women with HIV. We sought to: 1) describe the prevalence and grade of anal dysplasia and HPV infection in our study subjects; 2) analyze the grade of correlation between anal cytology, PCR of high-risk HPV, and histology; 3) identify the factors associated with the appearance of ≥ AIN2 lesions. DESIGN: Cross-sectional, prospective study. METHODS: A cohort of HIV-positive males (n = 140, mean age  = 37 years) who have sex with males (MSM) had epidemiological, clinical and analytical data collected. Anal mucosa samples were taken for cytology, HPV PCR genotyping, and anoscopy for histological analysis. RESULTS: Within the cohort, 77.1% were being treated with ART, 8.5% anoscopy findings were AIN2, and 11.4% carcinoma in situ; 74.2% had high-risk (HR), 59.7% low-risk (LR) HPV genotypes and 46.8% had both. The combination of cytology with PCR identifying HR-HPV better predicts the histology findings than either of these factors alone. Logistic regression highlighted ART as a protective factor against ≥ AIN2 lesions (OR: 0.214; 95%CI: 0.054-0.84). Anal/genital condylomas (OR: 4.26; 95%CI: 1.27-14.3), and HPV68 genotype (OR: 10.6; 95%CI: 1.23-91.47) were identified as risk factors. CONCLUSIONS: In our cohort, ART has a protective effect against dysplastic anal lesions. Anal/genital warts and HPV68 genotype are predictors of ≥ AIN2 lesions. Introducing PCR HPV genotype evaluation improves screening success over that of cytology alone.


Assuntos
Doenças do Ânus/complicações , Doenças do Ânus/patologia , Infecções por HIV/complicações , Homossexualidade Masculina , Adulto , Terapia Antirretroviral de Alta Atividade , Doenças do Ânus/epidemiologia , Doenças do Ânus/prevenção & controle , Coinfecção , Estudos Transversais , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV , Humanos , Hiperplasia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Proctoscopia , Curva ROC , Fatores de Risco , Adulto Jovem
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