ABSTRACT
Since December 2019, many drugs have been evaluated or advocated as potential treatments of SARS-CoV-2 induced disease (COVID-19), including many repositioned drugs and some others specifically developed for these diseases. They can be roughly classified into three categories according to their main mechanism of action (passive immunization, direct antivirals, and anti-inflammatory treatments), and their use depends on the stage of the disease. Despite often promising preclinical data, most of the treatments evaluated failed to show a significant clinical benefit. In addition, a few others have seen their effectiveness affected by the occurrence of SARS-CoV-2 variants and sub-variants. Herein, the aim of this article is to take stock of the data available as of the 14th of July 2022, concerning the specific healing options evaluated for patients suffering from COVID-19. We focus particularly on healing treatments of COVID-19 and do not deal with preventive treatments such as vaccine. Associated therapies such as venous thromboembolism prophylaxis are not detailed since they are covered in a specific chapter of this issue. Passive immunization, especially through monoclonal antibodies, showed a positive impact on the clinical evolution, whether in outpatients or inpatients without oxygen supply. However, their effectiveness strongly depends on the type of SARS-CoV-2 variant, and often decreases or even vanishes with the most recent variants. Among direct antiviral treatments, ritonavir-boosted nirmatrelvir appears to currently be the cornerstone in the management of early infections, but its use may be limited by drug interactions. Remdesivir remains as an alternative in this situation, even though it is potentially less convenient. Anti-inflammatory treatments have often been shown to be the most effective in inpatients with oxygen supply. Dexamethasone is now a cornerstone of management of these patients. Added tocilizumab seems beneficial in the case of hyper inflammation. JAK inhibitors and anakinra have also gained an interest in some studies. As a conclusion of this narrative review, the best treatment strategy has yet to be defined and is likely to evolve in the future, not only because many other drugs are still under development and evaluation, but also because of the viral epidemics and epidemiology evolution.
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Background: Vascular graft infection (VGI) remains a severe disease with high mortality and relapse rates. We performed a retrospective single-center cohort study to highlight factors associated with long-term all-cause mortality in patients with vascular graft infection. Methods: All patients hospitalized in our facility over 10 years for VGI were included. VGI was defined by the presence of a vascular graft or an aortic stent graft (stent or fabric), associated with 2 criteria among clinical, biological, imaging, or microbiological elements in favor of VGI. The primary outcome was all-cause mortality. Empirical antibiotic therapy was considered as appropriate when all involved pathogens were susceptible in vitro to the antibiotics used. The surgical strategy was defined as nonoptimal when the graft was not removed in a late-onset surgery (>3 months) or no surgery was performed. Results: One hundred forty-six patients were included. Empirical antibiotic therapy was administered in 98 (67%) patients and considered appropriate in 55 (56%) patients. Surgery was performed in 136 patients (96%) and considered as optimal in 106 (73%) patients. In multivariable analysis, appropriate empirical antibiotic therapy was associated with a lower probability of mortality (hazard ratio, 0.47 [95% confidence interval, .30-.79]; Pâ =â .002). Long-term survival did not differ according to whether the surgical strategy was considered optimal or not (log-rankâ =â 0.66). Conclusions: Appropriate empirical antibiotic therapy is a cornerstone of the management of VGI. Whenever possible, antibiotics must be associated with optimal surgical management. However, surgery could potentially be avoided in comorbid patients who are treated with appropriate antibiotics.
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During an epidemic period, we compared patients hospitalized for initial suspicion of COVID-19 but for whom an alternative diagnosis was finally retained (n = 152) with those who had COVID-19 (n = 222). Most common diagnoses were another infectious disease and heart failure. COVID-19-negative patients were more often active smokers had less often cough, fever, and digestive symptoms, as compared to the 222 COVID-19-positive patients. They had higher median neutrophil and lymphocyte counts and lower CRP level. In multivariate analysis, no current smoking, neurocognitive disorder, myalgia, and fibrinogen ≥4g/L were independently associated with a final diagnosis of COVID-19.
Subject(s)
COVID-19/diagnosis , Adult , Aged , COVID-19/therapy , COVID-19/virology , Hospitalization , Humans , Male , Patients/statistics & numerical data , Retrospective Studies , SARS-CoV-2/physiologyABSTRACT
Cystic echinococcosis (CE) is a cosmopolitan parasitic zoonosis affecting more than one million people worldwide. In humans, primary bone CE is rare and involvement of E. ortleppi is very uncommon. We report here the first case of primary vertebral cystic echinococcosis due to E. ortleppi in Burgundy, France.
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BACKGROUND: First-line antiretroviral therapy (1st ART) is an important step in a patient's management and often considered a long-term therapy at treatment initiation. METHODS: To describe the duration of 1st ART and the factors associated with treatment modification in a recent real-life setting, antiretroviral-naive patients who began their 1st ART in six French hospitals in 2009-2012 were included in a cohort. Clinical, immunological, virological and therapeutic data, as well as the reasons for therapeutic changes, if any, were retrospectively collected. RESULTS: A total of 206 patients started 1st ART, mainly a protease inhibitor-based triple therapy (73%), with a tenofovir-including backbone (87%). Of these, 89 (43%) had their 1st ART modified after a median of 16.5 months (IQR 8.0-32.8). Having a CD4+ T-cell count <200 cells/mm3, being pregnant, or 1st ART including zidovudine + lamivudine or lopinavir/r were significantly associated with a higher risk for treatment modification in multivariate analysis. In 47 patients (53%), 1st ART was modified for safety reasons, with no significant association with a given antiretroviral drug or class. No significant difference in virological, immunological and clinical outcomes was observed between the patients who had their 1st ART modified and those who did not. CONCLUSIONS: The proportion of modifications of the 1st ART during the first 2 years remains high. These modifications are frequently because of safety issues and the willingness to simplify treatment, and less often driven by virological failure, thus emphasizing that 1st ART is not - or is no longer - a lifelong treatment.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Adult , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV Infections/virology , Humans , Male , Middle Aged , Time FactorsABSTRACT
The use of TNFα antagonists must follow specific guidelines to ensure optimal effectiveness and safety. The French Society for Rheumatology (SFR) and Task Force on Inflammatory Joint Diseases (CRI), in partnership with several French learned societies, asked the French National Authority for Health (HAS) to develop and endorse good practice guidelines for the prescription and monitoring of TNFα antagonist therapy by physicians belonging to various specialties. These guidelines were developed, then, validated by two multidisciplinary panels of experts based on an exhaustive review of the recent literature and in compliance with the methodological rules set forth by the HAS. They pertain to the initial prescription of TNFα antagonists and to a variety of clinical situations that can arise during the follow-up of patients receiving TNFα antagonists (infections, malignancies, pregnancy, vaccination, paradoxical adverse events, surgery, use in older patients, and vasculitides).
Subject(s)
Antirheumatic Agents/therapeutic use , Autoimmune Diseases/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Humans , Inflammatory Bowel Diseases/drug therapyABSTRACT
BACKGROUND: Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. METHODS: A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone markers evaluations. RESULTS: Ninety-five (36%) patients had SHD. In univariate analysis, a significant and positive association was found between SHD and IL6 (p = 0.001), hsCRP (p = 0.04), increased serum C-Telopeptides X (CTX) (p = 0.005) and Parathyroid Hormon (PTH) (p < 0.0001) levels. In multivariate analysis, SHD deficiency correlated significantly with increased IL-6, high serum CTX levels, lower mean daily exposure to the sun, current or past smoking, hepatitis C, and functional status (falls), but not with the time spent on the current HAART (by specific drug or overall). CONCLUSIONS: SHD is frequent and correlates with inflammation in HIV infected patients. Since SHD is also associated with falls and increased bone catabolism, it may be of interest to take into account not only the type of antiretroviral therapy but also the residual inflammation on HAART in order to assess functional and bone risks. This finding also suggests that vitamin D supplementation may be beneficial in these HIV-infected patients.
Subject(s)
HIV Infections/complications , HIV Infections/metabolism , Inflammation Mediators/metabolism , Vitamin D Deficiency/etiology , Vitamin D Deficiency/metabolism , Adult , Aged , Antiretroviral Therapy, Highly Active , Biomarkers/metabolism , Bone and Bones/metabolism , Female , HIV Infections/drug therapy , Humans , Male , Middle Aged , Risk Factors , Young AdultABSTRACT
BACKGROUND: The match between the real-life therapeutic management of chronic hepatitis B (CHB) in HIV-infected patients and the recommendations that existed at the time has never been assessed on a case-by-case basis. METHODS: A total of 73 HBV-HIV coinfected patients, 34 of whom were first followed in 2003-2005 and 39 in 2006-2008 (before and after the 2005 European Consensus Conference on the treatment of chronic viral hepatitis in HIV coinfected patients), were included. All the data were retrospectively collected from their first visit to October 2008 through a standardised questionnaire. RESULTS: Baseline HBV DNA quantification and/or liver histology were missing in 44.1 and 28.2% of cases before and after 2005, respectively (p = 0.16). The observed management significantly differed from the recommendations for the whole population (p = 0.009), for the 2003-2005 group (p = 0.02), and tended to differ for the 2006-2008 group (p = 0.07). Therapeutic management of CHB was in accordance with the recommendations in 27 (57.4%) cases, with a higher rate of untreated patients in the 2003-2005 group, and a high rate of patients on dual therapy in both groups despite the fact that HBV therapy was not recommended. CONCLUSION: Even though global management of HBV-HIV coinfected patients is improving, baseline evaluation of CHB though necessary is still often insufficient. The strong rationale for early dual anti-HIV and anti-HBV therapy, and the reality of everyday clinical practice, bring support to the recent simplification of the recommendations widening the use of tenofovir and emtricitabine in HBV-HIV coinfected patients, irrespective of immunological, virological, or histological considerations.
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OBJECTIVE: To investigate the relationship between response to antiretroviral therapy (ART), alcohol use and occurrence of a major coronary or other arterial disease event (CADE) in HIV-infected individuals. DESIGN: A cohort study. A Cox model was used to identify the correlates of a first occurrence of a major CADE. SETTING: The French ANRS CO8 APROCO-COPILOTE cohort was set up in 1997 to study clinical progression and patient-reported outcomes (PRO) after initiating a protease inhibitor-containing ART. Clinical data were retrieved from medical records. Self-administered questionnaires collected data on PRO and behaviours, including alcohol use. PARTICIPANTS: Metabolic data were only available for a subgroup (n=675) of the study group (n=1154). MAIN OUTCOME MEASURES: Major coronary or other arterial disease first event. RESULTS: Over the 11-year follow-up, 49 major CADE were observed, with an incidence rate (95% CI)=0.75(0.57 to 0.99) per 100 person-years. Immunodepression (CD4 cell count <200 cells/mm(3)) was associated with an increased risk of CADE (adjusted HR (95% CI)=2.52(1.15 to 5.48)) after adjustment for female gender (0.25(0.08 to 0.83)), age (1.07(1.04 to 1.10)) and smoking>20 cigarettes/day (4.19(2.17 to 8.11)). Moreover, individuals with moderate alcohol consumption (≤4(3) alcohol units (AU)/day for men(women)) had a lower risk of CADE (0.38(0.20 to 0.71)) than alcohol abstainers, although the risk for those drinking>4(3) AU/day for men(women) was not significantly different from this latter group. These associations remained valid after adjustment for metabolic disorders. No significant association with exposure to any specific antiretroviral was detected. CONCLUSIONS: In the long term, absence of immunodepression and moderate alcohol consumption remain associated with a lower risk of a major CADE. Combined interventions to reduce CADE-risk-related behaviours including adherence counselling for assuring long-term immunological response to ART in HIV-infected individuals are now a clinical and public health priority.
Subject(s)
AIDS-Related Opportunistic Infections/pathology , Histoplasmosis/pathology , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/epidemiology , Antifungal Agents/administration & dosage , Dermis/pathology , Drug Therapy, Combination , Histoplasmosis/drug therapy , Histoplasmosis/epidemiology , Humans , Immune Reconstitution Inflammatory Syndrome/epidemiology , Male , Middle Aged , Pneumocystis carinii , Pneumonia, Pneumocystis/epidemiologyABSTRACT
Syphilitic ocular involvement is thought to be rare in HIV infected patients. During a 5-year study in 509 HIV-positive patients, syphilis was diagnosed in 3.9%, and the eye was involved in one-fifth of these. The high risk for sequelae emphasizes the need for prevention and for early diagnosis.