RESUMO
BACKGROUND: The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. METHODS: Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. RESULTS: We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8-47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0-44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00-6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18-3.36), platelet count < 100,000/µl (HR = 1.75; 95% CI 1.08-2.85) and increased INR (HR = 2.41; 95% CI 1.51-3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p = 0.83). CONCLUSIONS: Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease.
Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Cirrose Hepática/virologia , Idoso , Coinfecção/tratamento farmacológico , Feminino , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/tratamento farmacológico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
Recently, a significant cluster of pneumonia caused by a novel betacoronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) was described initially in China and then spread throughout the world. Like other coronaviridae, the viral transmission occurs mainly through droplets. In addition, the virus has been detected in different clinical specimens, suggesting a potential transmission by other routes, including blood transfusion. However, the potential risk of transmission of SARS-CoV-2 via blood products is still unclear. The aim of our study was to investigate the prevalence of antibodies against SARS-CoV-2 among blood donors from South-Eastern Italy. Moreover, in the seropositive donors, we searched for the presence of the virus in nasopharyngeal swabs and in plasma samples. Overall, 1,797 blood donors from the Apulia region were tested for anti-SARS-CoV-2 antibodies, using a commercially available assay. Only 18/1,797 donors (1.0%) tested positive for anti-SARS-CoV-2 antibodies; in none of them SARS-CoV-2 viral RNA was detected in nasopharyngeal swabs and in plasma samples. Our results indicate that most of the blood donors in Apulia remained uninfected during this wave of the pandemic; further, none had detectable virus both in nasopharyngeal swabs and in blood samples. The risk to carry and transmit the virus by healthy and asymptomatic blood donors is probably very low.
Assuntos
Anticorpos Antivirais/sangue , Doadores de Sangue , COVID-19/patologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , COVID-19/virologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , RNA Viral/análise , RNA Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Carga Viral , Adulto JovemRESUMO
Currently, treatment of chronic hepatitis C is based on a combination of direct-acting antiviral agents (DAAs) which achieve HCV clearance in more than 95% of patients. Despite this high rate of cure, treatment failures can occur in about 3-5% of treated patients. Resistance associated substitutions (RAS) are commonly detected after virological failure, although their role in real-life DAA failures is still debated. This study aimed to evaluate in real-life DAA-failing patients the prevalence of clinically relevant RASs for the different DAA classes and to identify possible predictors. Fifty consecutive HCV-infected patients who experienced a virological failure to a DAA-containing regimen were included in the study. Direct sequencing of HCV regions involved in DAA resistance (NS3, NS5A and NS5B) was performed with Sanger-based homemade protocols. The presence of mutations in the NS3 and NS5A regions was statistically associated with regimens containing protease inhibitors (p<0.0032) and NS5A inhibitors (p<0.0006), respectively. On the contrary, for the NS5B region, the known mutations associated with the NS5B RNA polymerase inhibitors were detected in treated HCV patients, although there was no statistical significance (p>0.5). A significant correlation was found between the presence of RASs and advanced fibrosis/cirrhosis, but not with age, sex and viral load. Our study demonstrates a high frequency of RASs in patients with DAA failure, thus highlighting the usefulness of genotypic tests in this setting. The identification of RASs may guide the choice of the most appropriate drugs for HCV re-treatment.
Assuntos
Antivirais , Hepatite C Crônica , Antivirais/farmacologia , Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Mutação , Falha de Tratamento , Proteínas não Estruturais Virais/genéticaRESUMO
Data on the long-term durability of rilpivirine (RPV) are still scarce. A two-center retrospective study was performed, including all people living with HIV (PLWH) treated with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)/RPV or tenofovir alafenamide (TAF)/FTC/RPV in the period January 2013-December 2019. Aims of the study were to assess the rate of discontinuation of the RPV single-tablet regimen (STR) and identify factors associated with the risk of discontinuation according to Cox's regression analysis. A total of 684 PLWH were enrolled. Mean duration of RPV-STR treatment was 192.5 (±99.5) weeks for 123 antiretroviral therapy (ART)-naïve participants (18%) and 173.3 (± 85.6) weeks for 561 ART-experienced study participants (82%). During the study period, the incidence of discontinuation was 7.7 per 100 person-years. The estimated proportions of discontinuation after 48 and 96 weeks were 5.6% and 13.4%, respectively. Causes of discontinuation were loss to follow-up (30%), side effects (15%), ART optimization (14%), virological failure (VF) (12%), death or transfer to another center (9%), low adherence (7%), drug interactions (6%), simplification to dual therapy (3%), and unknown (3%). No differences were observed in cumulative probability of discontinuation between ART-naïve and -experienced PLWH. Heterosexual (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.4-6.8) and mother-to-child (HR 5.3, 95% CI 1.8-15.3) transmission of HIV infection and history of previous VF (HR 1.7, 95% CI 1.2-2.5) were associated with higher risk of discontinuation. High RPV-STR effectiveness and durability were confirmed in our real-life population of PLWH. Given these data, RPV has the potential to be a drug for life in patients selected according to current guidelines.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Transmissão Vertical de Doenças Infecciosas , Estudos Retrospectivos , Rilpivirina/farmacologia , Rilpivirina/uso terapêutico , Comprimidos , Tenofovir/farmacologia , Tenofovir/uso terapêuticoRESUMO
Is it possible to achieve a collaboration between Infectious Diseases (ID) Specialists and General Practitioners (GPs) in the management of chronic HIV infection? A cross sectional survey was conducted among People Living with HIV (PLWHIV) attending the outpatient services of four Italian Infectious Diseases Centers to understand to which extent patients trust their GPs and involve them in the management of their chronic condition. Information about level of communication with GPs, subjective perception of the disease, and presence of co-medications were collected and matched with socio-demographic data using χ2statistics. A p<0.05 was considered statistically significant. From December 2019 to February 2020, 672 patients completed the survey, 59% males and 56% >50 years. Overall, 508 patients (76%) had informed GPs about HIV-positivity. Communication of diagnosis was significantly associated with age >50years, lower education level, history of disease >10 years and residency in Northern Italy. The "Undetectable = Untrasmittable" (U = U) concept was investigated as an indirect measure of perceived stigma. 23% of subjects was unaware of its meaning. Despite undetectable status, 50% of PLWHIV found difficult to communicate their condition to GPs, especially married (52% vs 48% of unmarried, p = 0.003), well-educated patients (51% vs 48, p = 0.007), living in Southern vs Northern Italy (52% vs 46%, p< 0.001). More than 75% of the participants consulted the ID specialist for co-medications and DDIs management, often complaining a lack of communication of the former with GPs. Overall, a good level of communication between PLWHIV and GPs was outlined, even if a wider involvement of the latter in HIV care is desirable.
Assuntos
Clínicos Gerais , Infecções por HIV , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of this study is to describe the features, the outcomes, and the clinical issues related to Remdesivir administration of a cohort of 220 patients (pts) with COVID-19 hospitalized throughout the last two pandemic waves in Italy. One hundred and nine pts were enrolled from 1 September 2020, to 28 February 2021 (Group A) and 111 from 1 March to 30 September 2021 (Group B). Notably, no differences were reported between the two groups neither in the timing of hospitalization. nor in the timing of Remdesivir administration from symptoms onset. Remarkably, a higher proportion of pts with severe COVID-19 was observed in Group B (25% vs. 10%, p < 0.001). At univariate and multivariate analysis, rather than the timing of Remdesivir administration, age, presence of coexisting conditions, D-dimers, and O2 flow at admission correlated positively to progression to non-invasive ventilation, especially for patients in Group B. However, the rate of admission in the Intensive Care Unit and/or death was comparable in the two groups (7% vs. 4%). Negligible variations in serum GOT, GPT, GGT, and eGFR levels were detected. A mean reduction in heart rate was noticed within the first three days of antiviral treatment (p < 0.001). Low rate of ICU admission, high rate of clinical recovery, and good drug safety were observed in COVID-19 patients treated with Remdesivir during two diverse pandemic waves.