There is no known effective oral therapy for early COVID-19. This randomized trial evaluated effects of oral hydroxychloroquine on symptoms and disease severity in adult outpatients with early COVI... Visual Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 There is no known effective oral therapy for early COVID-19. This randomized, double-blind, placebo-controlled trial... Background: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19). Objective: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients....

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series, and public figure endorsements. While there is a growing body of scientific data, there is also concern for harm, particularly QTc prolongation and cardiac arrhythmias. Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines.

Amphotericin B deoxycholate (AMB) has substantial toxicities. A novel encochleated amphotericin B deoxycholate (cAMB) formulation has oral bioavailability, efficacy in an animal model, and minimal toxicity due to targeted drug delivery into macrophages, where intracellular fungi reside. We conducted a phase I, ascending-dose trial of cAMB administered at 1.0 g, 1.5 g, or 2.0 g per day in 4 to 6 divided doses among HIV-positive survivors of cryptococcosis ( n = 9 per cohort).

Background: Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials. Methods: We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. Results: We enrolled 2795 participants. The median age of research participants (interquartile range) was 40 (34–49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and 748 (29%) reported at least 1 medication side effect. Side effects were reported in 40% with once-daily, 36% with twice-weekly, 31% with once-weekly hydroxychloroquine, compared with 19% with placebo. The most common side effects were upset stomach or nausea (25% with once-daily, 19% with twice-weekly, and 18% with once-weekly hydroxychloroquine, vs 11% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for once-daily, 17% twice-weekly, and 13% once-weekly hydroxychloroquine, vs 7% for placebo). Two individuals were hospitalized for atrial arrhythmias, 1 on placebo and 1 on twice-weekly hydroxychloroquine. No sudden deaths occurred. Conclusions: Data from 3 outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials, in cohorts of healthy outpatients, can safely investigate whether hydroxychloroquine is efficacious for COVID-19. ClinicalTrials.gov Identifier: NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for pre-exposure prophylaxis trial.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel pathogen causing the current worldwide coronavirus disease 2019 (COVID-19) pandemic. Due to insufficient diagnostic testing in the United States, there is a need for clinical decision-making algorithms to guide testing prioritization. We recruited participants nationwide for a randomized clinical trial. We categorized participants into 3 groups: (1) those with confirmed SARS-CoV-2 infection, (2) those with probable SARS-CoV-2 infection (pending test or not tested but with a confirmed COVID-19 contact), and (3) those with possible SARS-CoV-2 infection (pending test or not tested and with a contact for whom testing was pending or not performed). We compared the frequency of self-reported symptoms in each group and categorized those reporting symptoms in early infection (0–2 days), midinfection (3–5 days), and late infection (>5 days). Among 1252 symptomatic persons screened, 316 had confirmed, 393 had probable, and 543 had possible SARS-CoV-2 infection. In early infection, those with confirmed and probable SARS-CoV-2 infection shared similar symptom profiles, with fever most likely in confirmed cases (P = .002). Confirmed cases did not show any statistically significant differences compared with unconfirmed cases in symptom frequency at any time point. The most commonly reported symptoms in those with confirmed infection were cough (82%), fever (67%), fatigue (62%), and headache (60%), with only 52% reporting both fever and cough. Symptomatic persons with probable SARS-CoV-2 infection present similarly to those with confirmed SARS-CoV-2 infection. There was no pattern of symptom frequency over time.

SUMMARY: Cryptococcal meningitis is a leading cause of morbidity and mortality globally, especially in people with advanced HIV disease. Cryptococcal meningitis is responsible for nearly 20% of all deaths related to advanced HIV disease, with the burden of disease predominantly experienced by people in resource-limited countries. Major advancements in diagnostics have introduced low-cost, easy-to-use antigen tests with remarkably high sensitivity and specificity. These tests have led to improved diagnostic accuracy and are essential for screening campaigns to reduce the burden of cryptococcosis. In the last 5 years, several high-quality, multisite clinical trials have led to innovations in therapeutics that have allowed for simplified regimens, which are better tolerated and result in less intensive monitoring and management of medication adverse effects. One trial found that a shorter, 7-day course of deoxycholate amphotericin B is as effective as the longer 14-day course and that flucytosine is an essential partner drug for reducing mortality in the acute phase of disease. Single-dose liposomal amphotericin B has also been found to be as effective as a 7-day course of deoxycholate amphotericin B. These findings have allowed for simpler and safer treatment regimens that also reduce the burden on the healthcare system. This review provides a detailed discussion of the latest evidence guiding the clinical management and special circumstances that make cryptococcal meningitis uniquely difficult to treat.