Coronavirus, uses the Angiotensin Converting Enzyme-2 Receptor to enter airway cells. Viral endocytosis is mediated by several factors, including clathrin, the adaptor protein-2 complex (AP2) and the adaptor-associated kinase-1 (AAK1). 2 According to a recent report, 3 COVID-19, the disease caused by SARS-CoV-2, is characterized by three clinical patterns: no symptoms, mild to moderate disease, severe pneumonia requiring admission to Intensive Care Unit (ICU) in up to 31% of the patients. 3 Thus far, there is no specific therapy for COVID-19 infection. No benefit of lopinavir-ritonavir treatment resulted in a recent trial. 4 Hydroxychloroquine, currently used in view of its "in vitro" observed effect of reduction of viral replication, seems unsatisfactory. 5 Elevated proinflammatory cytokine/chemokine responses seem associated with respiratory failure. 3 Recently, tocilizumab, an interleukin-6 inhibitor, was reported as effective in patients with severe COVID-19 pneumonia. 6 Baricitinib, another inhibitor of cytokine-release, seems an interesting anti-inflammatory drug. It is a Janus kinase inhibitor (anti-JAK) licensed for the treatment of rheumatoid arthritis (RA) with good efficacy and safety records. 7 Moreover it seems to have anti-viral effects by its affinity for AP2-associated protein AAK1, reducing SARS-CoV-2 endocytosis. 8 On this basis, we assessed the safety of baricitinib therapy combined with lopinavir-ritonavir in moderate COVID-19 pneumonia patients and we evaluated its clinical impact.All consecutive hospitalized patients (March 16th −30th) with moderate COVID-19 pneumonia, older than 18 years, were treated for 2 weeks with baricitinib tablets 4 mg/day added to ritonavir-lopinavir therapy. The last consecutive patients with moderate COVID-19 pneumonia receiving standard of care therapy (lopinavir/ritonavir tablets 250 mg/bid and hydroxychloroquine 400 mg/day/orally for 2 weeks) admitted before the date of the first baricitinib-treated patient served as controls. Antibiotics were scheduled only in the case of suspected bacterial infection.Inclusion criteria were: a. SARS-Co-V2 positivity in the nasal/oral swabs; b. presence of at least 3 of the following symptoms: fever, cough, myalgia, fatigue; c. evidence of radiological pneumonia . After discharge, patients treated with baricitinib were planned to be followed for additional 6 weeks. Exclusion criteria: history of thrombophlebitis (TP), latent tuberculosis infection (QuantiFERON Plus-test positivity, Qiagen, Germany 9 ), pregnancy and lactation.Mild to moderate COVID-19 disease definition: presence of bilateral pneumonia with or without ground glass opacity and in absence of consolidation, not requiring intubation at enrollment; arterial oxygen saturation (SpO2) > 92% at room-air, and ratio arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO2) 10 0-30 0 mmHg. Parameters daily accessed were: fever, pulmonary function, Modified Early Warning Score (MEWS), 10 pulse rate, blood pressure. After the initial execution, r...
Sexually acquired hepatitis C virus (HCV) infection remains a public health problem, with significant disease burden primarily in HIV-positive men who have sex with men (MSM). Over the past decades, the epidemic of sexually transmitted HCV infection has continued to expand and the epidemiology of HCV in HIV has changed significantly. In the post-combination antiretroviral therapy era, sexual network characteristics within the specific core group of MSM with increased sexual risk behaviours, including serosorting on the basis of HIV-positive status and intense mucosally traumatic sexual practices, confer increased HCV acquisition and transmission. This review summarizes the current epidemiology of sexually acquired HCV infection and the clinical and immunological contexts of acute HCV infection, and describes the biological, social, and behavioural factors that have facilitated permucosal transmission of HCV in MSM. While the advent of direct-acting antivirals has improved treatment responses significantly, sexually transmitted HCV reinfections occur in a substantial proportion of HIV-positive MSM following clearance of a primary infection. Effective strategies and preventive interventions that are tailored to the MSM communities to facilitate the control of sexually acquired HCV infection cannot be overemphasized.
IntroductionAlthough access to highly active antiretroviral therapy (HAART) has prolonged survival and improved life quality, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support in intensive care units (ICU). This study aimed to describe the etiology and analyze the prognostic factors of HIV-infected Taiwanese patients in the HAART era.MethodsMedical records of all HIV-infected adults who were admitted to ICU at a university hospital in Taiwan from 2001 to 2010 were reviewed to record information on patient demographics, receipt of HAART, and reason for ICU admission. Factors associated with hospital mortality were analyzed.ResultsDuring the 10-year study period, there were 145 ICU admissions for 135 patients, with respiratory failure being the most common cause (44.4%), followed by sepsis (33.3%) and neurological disease (11.9%). Receipt of HAART was not associated with survival. However, CD4 count was independently predictive of hospital mortality (adjusted odds ratio [AOR], per-10 cells/mm3 decrease, 1.036; 95% confidence interval [CI], 1.003 to 1.069). Admission diagnosis of sepsis was independently associated with hospital mortality (AOR, 2.91; 95% CI, 1.11 to 7.62). A hospital-to-ICU interval of more than 24 hours and serum albumin level (per 1-g/dl decrease) were associated with increased hospital mortality, but did not reach statistical significance in multivariable analysis.ConclusionsRespiratory failure was the leading cause of ICU admissions among HIV-infected patients in Taiwan. Outcome during the ICU stay was associated with CD4 count and the diagnosis of sepsis, but was not associated with HAART in this study.
Outbreaks of sexually transmitted hepatitis C virus (HCV) infections have been recently reported in HIV-
The incidence of and risk factors for Jarisch-Herxheimer (JH) reaction were investigated prospectively among 240 human immunodeficiency virus (HIV)-infected and 115 HIV-uninfected patients with syphilis who received penicillin treatment. The overall rate of JH reaction was 31.5% (34.6% in HIV-infected patients and 25.2% in HIV-uninfected patients). In multivariate analysis, risk factors for JH reaction included high rapid plasma reagin (RPR) titers (per log(2) RPR increase, risk ratio [RR], 1.19; 95% confidence interval [CI], 1.04-1.37), early syphilis (RR, 8.59; 95% CI, 4.75-15.56), and prior penicillin treatment (RR, 0.39; 95% CI, 0.20-0.78).
Between June 1994 and February 2003, a total of 111 human immunodeficiency virus (HIV)-infected patients with chronic hepatitis B virus (HBV) coinfection and 387 HIV-infected patients without HBV or hepatitis C virus coinfection were prospectively observed to assess the impact of HBV infection on outcomes of HIV-infected patients. After a median duration of observation of 25 months, coinfected patients were more likely to develop hepatitis (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [CI], 1.69-3.82) and hepatic decompensation (adjusted odds ratio [AOR], 9.94; 95% CI, 1.89-52.35). Although similar proportions of the 2 patient groups had an increase in the CD4 count by> or =100x10(6) cells/L (AOR, 0.78; 95% CI, 0.45-1.36) and development of new opportunistic illnesses (AOR, 0.94; 95% CI, 0.53-1.66), HBV-infected patients had an increased risk for virologic failure (AOR, 1.76; 95% CI, 1.03-2.99) and death (AHR, 1.71; 95% CI, 1.19-2.47) after highly active antiretroviral therapy was initiated.
To understand the Candida colonization of human immunodeficiency virus (HIV)-infected outpatients inTaiwan, we have conducted a prospective cohort study of Candida colonization and its risk factors at the National Taiwan University Hospital from 1999 to 2002. More than 50% of the patients were colonized with Candida species, and 12% developed symptomatic candidiasis. Patients colonized with fluconazole-resistant strains of Candida species had a higher prevalence of candidiasis than those colonized with susceptible strains. Our analysis found that antibiotic treatment and lower CD4؉ counts (<200 cells/mm 3 ) increased the rate of oropharyngeal candidiasis in HIV-infected patients, while antiretroviral therapy protected patients from the development of candidiasis.Mucosal candidiasis, including oropharyngeal, esophageal, and vaginal candidiasis, is common among human immunodeficiency virus (HIV)-infected patients (4, 11). In particular, oropharyngeal candidiasis occurs in up to 90% of patients during the course of HIV infection (17). Progressive cellmediated immunodeficiency, with CD4 ϩ lymphocyte counts less than 200 cells/mm 3 , is a risk factor for colonization with Candida species and the development of candidiasis (3). The widespread use of azole antifungal agents for the treatment of mucosal candidiasis results in colonization with less susceptible organisms and the development of resistance (4, 15). Thus, oropharyngeal candidiasis due to drug-resistant fungi is an emerging problem for patients infected with HIV (18).The overall prevalence of known HIV infection in Taiwan remains relatively low (0.01%) (9). As in most other industrialized countries, the majority of HIV-infected patients in Taiwan receive care in the outpatient setting. Therefore, to better understand the epidemiology of Candida species carriage among HIV-infected outpatients in Taiwan, we undertook a study to determine the prevalence of oropharyngeal colonization. Our objectives were to assess the colonization status and the risk factors for colonization and the development of candidiasis in HIV-infected outpatients in Taiwan. The susceptibilities of those Candida isolates to antifungal drugs were also determined. MATERIALS AND METHODSStudy population and data collection. HIV-infected patients were monitored regularly in the outpatient infectious diseases clinic of National Taiwan University Hospital, a major referral hospital for the management of HIV-related complications. The patients were enrolled after they provided informed verbal consent. This was a prospective study performed by the use of three surveys, conducted from May to June 1999, May to September 2001, and January to April 2002. A standardized data collection form was used to retrieve demographic information, the most recent CD4 ϩ lymphocyte count, and the highly active antiretroviral therapy (HAART) prescribed. In addition, clinical information for the previous 3 months was obtained and included information on whether the patient had a history of oral or esophageal candidiasi...
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