HIV-infected adults with chronic aminotransferase elevations while receiving ART have a high rate of liver disease. Noninvasive testing can help identify liver disease in such patients, but liver biopsy is necessary to definitively identify those at risk for liver disease progression and complications. Longitudinal follow-up of this cohort will better characterize the natural history of aminotransferase elevations in this population and identify noninvasive biomarkers of liver disease progression.

HIV-infected patients are at approximately 100-fold greater risk of developing osteonecrosis than the general population. Disease progression is slower in asymptomatic patients than in symptomatic patients. Given the high frequency of total hip replacement in symptomatic patients, studies to assess preventive and treatment strategies are essential.

IMPORTANCE Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear.OBJECTIVE To determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19-related symptoms among nonhospitalized participants with symptomatic COVID-19 infection.DESIGN, SETTING, AND PARTICIPANTS This phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020.INTERVENTIONS Participants were randomly assigned to receive ciclesonide MDI, 160 μg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 μg) or placebo for 30 days.MAIN OUTCOMES AND MEASURES The primary end point was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19.RESULTS A total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19-related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study. CONCLUSIONS AND RELEVANCEThe results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19-related symptoms.TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04377711

Over the past 10 years, in conjunction with the broad availability of potent antiretroviral regimens, the care of human immunodeficiency virus (HIV)-infected patients has shifted from prevention and treatment of opportunistic infections and malignancies to management of the metabolic and related complications associated with HIV infection and its treatment. Metabolic disorders, including lipodystrophy, dyslipidemia, and insulin resistance, occur at a high rate in HIV-infected individuals receiving highly active antiretroviral therapy (HAART). These disorders are associated with increased risk of cardiovascular disease and have become an important cause of morbidity and mortality in HIV-infected patients. Herein, we present the case of a patient with HIV infection who responded well to HAART but developed multiple complications potentially related to this therapy. This article reviews the clinical characteristics of the metabolic and skeletal disturbances observed in HIV infection and discusses strategies for their management.

Background Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective anti-fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed. Aim To study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in subjects with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection and advanced liver disease. Methods Eighteen subjects with advanced liver fibrosis received simtuzumab 700mg intravenously every 2 weeks for 22 weeks. Transjugular liver biopsies were performed during screening and at the end of treatment to measure hepatic venous pressure gradient (HVPG) and to stage fibrosis. Results Treatment was well-tolerated with no discontinuations due to adverse events. No significant changes were seen in HVPG or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsy and serum samples suggested up-regulation of TGF-β3 and IL-10 pathways with treatment. Conclusion In this open-label, pilot clinical trial, simtuzumab treatment was well-tolerated in HCV- and HIV-infected subjects with advanced liver disease. Putative modulation of TGF-β3 and IL-10 pathways during simtuzumab treatment merits investigation in future trials.

HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART.

OBJECTIVE Hydrogen-1 MR spectroscopy (1H-MRS) is gaining acceptance as a noninvasive technique for assessment of hepatic steatosis, and the findings have been found to correlate closely with histopathologic grade. The aims of this study were to validate 1H-MRS performed with a 3-T MRI system for quantifying hepatic steatosis and to determine threshold values of 1H-MRS proton density fat fraction corresponding to standard histopathologic grade in patients undergoing diagnostic liver biopsy. SUBJECTS AND METHODS We conducted a prospective cross-sectional liver MRS study with 52 subjects undergoing diagnostic liver biopsy. The diagnostic accuracy of 1HMRS was evaluated with receiver operating characteristic curves. RESULTS The diagnostic accuracy of 1H-MRS for hepatic steatosis was high with an area under the receiver operating characteristic curve of 0.94 (95% CI, 0.88–1.0). Results were similar for three 1H-MRS measurements obtained at different locations in the liver, for two independent pathologists, and whether fibrosis was present or absent. One third of participants had elevated transaminase concentrations of unknown cause, and 1H-MRS estimates of steatosis had perfect agreement with histopathologic grade in this group. Calculated 1H-MRS proton density fat fraction thresholds for histologic grades were less than 17% for grade 0 or trace steatosis, 17–38.6% for grade 1, and greater than 38.6% for grade 2 or higher. CONCLUSION Hydrogen-1 MR spectroscopy is an effective, noninvasive technique that can be used to diagnose and quantify hepatic steatosis. Hydrogen-1 MR spectroscopy thresholds corresponded with histopathologic grades and may be useful in the workup of patients with elevated transaminase concentrations.

ABSTRACT. Objective. The increase in asthma prevalence has been documented worldwide, affecting many races living in many different climates. Multiple studies have demonstrated that the most striking prevalence and morbidity of asthma in the United States has been in black children, but little research has determined the scale of the increase, or specifically when the disease became severe in this group. This study sought to determine exactly when the rise in asthma hospitalizations among black patients began and what the pattern of asthma hospitalizations has been in different races and age groups over a 40-year period in 1 urban area.Methods. A retrospective chart review of discharges from the Medical University of South Carolina was conducted from 1956 to 1997. Charts with the primary discharge diagnosis of asthma were examined for discharge date, race, and age group (0-to 4-year-olds, 5-to 18-yearolds, 19-to 50-year-olds, >51-year-olds). The diagnostic codes used were based on the International Classification of Diseases (ICD)-6, 1956 -1957; ICD-7, 1958 -1967; ICD-8, 1968 -1978; and ICD-9, 1979 -1997. Over the period studied, this hospital was the primary inpatient provider for children in this area, and the only provider for uninsured children. Between 1960 and 1990, the racial makeup of the area remained stable, as did the percentage of blacks living at the poverty level. The raw number of asthma discharges, rate per 10 000 discharges of the same race, and rate per 100 000 population in Charleston County were tabulated for each age group and racial category.Results. Over the time period examined, there has been a progressive increase in asthma hospitalizations in black individuals of all age groups and in whites under 18 years. The most striking increase has been in black children 0 to 18 years old (Figure). The increase either as raw values or as a rate per 100 000 began around 1970, and was linear. This increase in black children discharged with asthma as a rate per 100 000 population was 20-fold: the rate increased from 18 in 1970 to 370 in 1997. Asthma discharges as a rate per 10 000 black children discharged increased by 24-fold from 1960 to 1997. Total discharges from the hospital increased from 49 000 to 128 000 per year over this period. Blacks made up only 28% of discharges in 1957, but that proportion increased to 56% in 1960 and remained relatively stable over the following 35 years. The increase seen in white children 0 to 18 years of age as a rate per 100 000 population was 5-fold and began around 1980. Both increases seem to be consistent over the time period studied, and continued to 1997.Conclusions. Among a predominantly poor black population living in a southern US city, there has been a steady increase in childhood asthma hospitalizations over the past 30 years. A significant although less dramatic rise has occurred in white children. Over this time period, although there have been many changes in lifestyle that could have contributed to this rise, there have been no major changes in hou...