RESUMEN

Spontaneously occurring resistance may impair the success of protease inhibitors based regimens in HCV treatment. This study aimed to evaluate associations between amino acid substitutions in NS3/NS4A domain and clinical features of 247 HCV mono or HCV/HIV co-infected patients. Fourteen samples (5.7%) harbored at least one resistance-associated substitution (RAS). The following RASs were detected in NS3 region: T54S (6-2.4%), V55A (7-2.8%), and Q80R (2-0.8%). S122G occurred in 86.9% of HCV genotype 1b samples with either natural polymorphisms or RASs. Advanced liver fibrosis and HIV co-infection were not related to NS3/NS4A amino acid substitutions.

Asunto(s)

Coinfección , Infecciones por VIH/complicaciones , Hepacivirus/genética , Hepatitis C Crónica/virología , Polimorfismo Genético , Proteínas no Estructurales Virales/genética , Adulto , Antivirales/uso terapéutico , Brasil/epidemiología , Farmacorresistencia Viral/genética , Femenino , Genotipo , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Hepacivirus/enzimología , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Mutación Missense , Inhibidores de Proteasas/uso terapéutico , Análisis de Secuencia de ADN

RESUMEN

Several studies have demonstrated that HIV/hepatitis C virus (HCV)-coinfected patients experience more rapid fibrosis progression. In this study, to estimate the annual rate of direct liver fibrosis progression, we used analyses of paired biopsy samples from HIV/HCV-coinfected patients without prior treatment of hepatitis and assessed the possible association of fibrosis progression with certain clinical variables. We evaluated 30 HIV/HCV-coinfected patients, with no history of prior treatment of hepatitis C, who underwent paired liver biopsies. All patients were under antiretroviral therapy at first and second biopsies. The average annual progression rate was 0.13 fibrosis unit/year, with 36.7% of patients defined as progressors. Liver fibrosis progression was associated with alanine aminotransferase (ALT; P < .001) and aspartate aminotransferase (AST; P < .0340) levels over 3 times the upper limit of normal present at first biopsy. Elevated ALT and AST levels appear to be associated with more accelerated liver fibrosis progression among HIV/HCV-coinfected patients.

Asunto(s)

Infecciones por VIH/patología , Hepatitis C/patología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Biopsia , Coinfección , Progresión de la Enfermedad , Femenino , Infecciones por VIH/enzimología , Infecciones por VIH/virología , Hepatitis C/enzimología , Hepatitis C/virología , Humanos , Hígado/patología , Cirrosis Hepática/enzimología , Masculino , Persona de Mediana Edad

RESUMEN

BACKGROUND: Nucleoside/nucleotide analogue (NA) treatment causes selection pressure for HBV strains carrying mutations conferring NA resistance. Drug-resistance mutations occur in the reverse transcriptase (RT) region of the HBV polymerase gene and spontaneously arise during viral replication. These mutations can also alter the hepatitis B surface (HBs) protein and in some cases reduce binding to HBs antibodies. The spread of NA-resistant HBV may impact the efficacy of antiviral treatment and hepatitis B immunization programmes. In this study, we used direct sequencing to assess the occurrence of HBV carrying known mutations that confer NA resistance in the largest cohort of treatment-naive patients with chronic hepatitis B (CHB) to date. METHODS: HBV DNA samples isolated from 702 patients were sequenced and the RT region subjected to mutational analysis. RESULTS: There was high genetic variability among the HBV samples analysed: A1 (63.7%), D3 (14.5%), A2 (3.3%), A3 (0.1%), B1 (0.1%), B2 (0.1%), C2 (0.9%), D1 (0.9%), D2 (4.6%), D4 (5.1%), D unclassified subgenotype (0.7%), E (0.6%), F2a (4.6%), F4 (0.4%) and G (0.4%). HBV strains harbouring mutations conferring NA resistance alone or combined with compensatory mutations were identified in 1.6% (11/702) of the patients. CONCLUSIONS: HBV strains harbouring resistance mutations can comprise the major population of HBV quasispecies in treatment-naive patients. In Brazil, there is a very low frequency of untreated patients who are infected with these strains. These findings suggest that the spread and natural selection of drug-resistant HBV is an uncommon event and/or most of these strains remain unstable in the absence of NA selective pressure.

Asunto(s)

Antivirales/farmacología , Farmacorresistencia Viral/genética , Productos del Gen pol/genética , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/virología , Mutación , Adenina/análogos & derivados , Adenina/farmacología , Anticuerpos Antivirales/genética , Anticuerpos Antivirales/inmunología , Brasil , ADN Viral/genética , ADN Viral/inmunología , Productos del Gen pol/antagonistas & inhibidores , Productos del Gen pol/metabolismo , Genotipo , Guanina/análogos & derivados , Guanina/farmacología , Antígenos de Superficie de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/inmunología , Humanos , Lamivudine/farmacología , Pruebas de Sensibilidad Microbiana , Organofosfonatos/farmacología , Estudios Retrospectivos , Análisis de Secuencia de ADN , Tenofovir/farmacología , Replicación Viral/efectos de los fármacos

RESUMEN

BACKGROUND: HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. METHODS: We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. RESULTS: HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. CONCLUSIONS: Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample.

Asunto(s)

Antivirales/uso terapéutico , Farmacorresistencia Viral , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Mutación , Inhibidores de Proteasas/uso terapéutico , Adulto , Brasil , Coinfección , Femenino , Infecciones por VIH , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Resultado del Tratamiento , Carga Viral , Proteínas no Estructurales Virales/genética

RESUMEN

Neurological complications represent one of the most important causes of morbidity and mortality in patients with HIV/AIDS. However, peripheral neuropathy comprises only 5% to 20% of the total neurological complications and facial nerve palsy, especially when it is bilateral, is a less common manifestation. Peripheral facial palsy has been considered as a possible neurological complication of the early stage of HIV infection but the number of reported cases in the literature is limited. Histological findings of nervous tissue in peripheral facial palsy at an early stage of HIV infection include a degenerative and not suppurative inflammatory process, but its etiology remains obscure. Peripheral facial palsy in the late stage of HIV infection is characterized by an advanced immunological deficit and generally it is secondary to an opportunistic infection of the CNS, such as neurotoxoplasmosis and lymphoma. However, this peripheral attack of the facial nerve is not very common at this late stage of HIV infection. Bilateral peripheral facial palsy as a complication of non-Hodgkin s lymphoma is considered an extremely rare entity. There are no published reports of bilateral peripheral facial palsy secondary to lymphomas or other neoplasms of the CNS in immunosuppressed patients. Non-Hodgkin s lymphoma (NHL) has been considered a late and relatively common manifestation of HIV infection, but an exact cause for the higher incidence of this malignant neoplasm in HIV/AIDS patients is still uncertain.

Asunto(s)

Parálisis Facial/complicaciones , Parálisis Facial/etiología , Infecciones por VIH/complicaciones , Linfoma no Hodgkin/complicaciones , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Parálisis Facial/líquido cefalorraquídeo , Infecciones por VIH/líquido cefalorraquídeo , Humanos , Linfoma no Hodgkin/líquido cefalorraquídeo , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Prednisona/uso terapéutico , Vincristina/uso terapéutico

RESUMEN

Neurological complications represent one of the most important causes of morbidity and mortality in patients with HIV/AIDS. However, peripheral neuropathy comprises only 5 to 20 of the total neurological complications and facial nerve palsy, especially when it is bilateral, is a less common manifestation. Peripheral facial palsy has been considered as a possible neurological complication of the early stage of HIV infection but the number of reported cases in the literature is limited. Histological findings of nervous tissue in peripheral facial palsy at an early stage of HIV infection include a degenerative and not suppurative inflammatory process, but its etiology remains obscure. Peripheral facial palsy in the late stage of HIV infection is characterized by an advanced immunological deficit and generally it is secondary to an opportunistic infection of the CNS, such as neurotoxoplasmosis and lymphoma. However, this peripheral attack of the facial nerve is not very common at this late stage of HIV infection. Bilateral peripheral facial palsy as a complication of non-Hodgkin s lymphoma is considered an extremely rare entity. There are no published reports of bilateral peripheral facial palsy secondary to lymphomas or other neoplasms of the CNS in immunosuppressed patients. Non-Hodgkin s lymphoma (NHL) has been considered a late and relatively common manifestation of HIV infection, but an exact cause for the higher incidence of this malignant neoplasm in HIV/AIDS patients is still uncertain.

Asunto(s)

Humanos , Masculino , Adulto , Parálisis Facial , Infecciones por VIH/complicaciones , Linfoma no Hodgkin/complicaciones , Ciclofosfamida , Doxorrubicina , Parálisis Facial , Infecciones por VIH/líquido cefalorraquídeo , Linfoma no Hodgkin/líquido cefalorraquídeo , Linfoma no Hodgkin/tratamiento farmacológico , Prednisona , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Vincristina

RESUMEN

Lesöes papilomatosas causadas pelo papilomavírus humano säo comumente encontradas em regiäo anogenital sob a forma de condilomas. Formas näo usuais podem ser encontradas em pacientes com grave imunodepressäo. Nesse relato de caso, um homem soropositivo para o HIV há 5 anos com contagem de células CD4 + de 0 células/mm, cursou com lesöes aftosas de aparecimento intermitente, disfagia e emagrecimento por oito meses

Asunto(s)

Humanos , Masculino , Adulto , Síndrome de Inmunodeficiencia Adquirida , Papillomaviridae