Factors Associated With Fecal Microbiota Transplant Failure in the Treatment of Recurrent Clostridioides difficile Infection: A Single-Center Retrospective Study.

Background infection (CDI) is a major cause of hospital-acquired diarrhea and is associated with substantial morbidity and mortality. Recurrences following treatment are common. Fecal microbiota transplantation (FMT) is a therapeutic intervention in which stool from a healthy donor is administered to a patient with recurrent CDI.

HIV post-treatment controllers have distinct immunological and virological features.

HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk.

Transcriptomic Signatures of Human Immunodeficiency Virus Post-Treatment Control.

Posttreatment controllers (PTCs) are rare HIV-infected individuals who can limit viral rebound after antiretroviral therapy interruption (ATI), but the mechanisms of this remain unclear. To investigate these mechanisms, we quantified various HIV RNA transcripts (via reverse transcription droplet digital PCR [RT-ddPCR]) and cellular transcriptomes (via RNA-seq) in blood cells from PTCs and noncontrollers (NCs) before and two time points after ATI. HIV transcription initiation did not significantly increase after ATI in PTCs or in NCs, whereas completed HIV transcripts increased at early ATI in both groups and multiply-spliced HIV transcripts increased only in NCs.

Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA).

Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated.

Frequency of post treatment control varies by antiretroviral therapy restart and viral load criteria.

Clinical trials including an analytical treatment interruption (ATI) are vital for evaluating the efficacy of novel strategies for HIV remissions. We briefly describe an interactive tool for predicting viral rebound timing in ATI trials and the impact of posttreatment controller (PTC) definitions on PTC frequency estimates. A 4-week viral load threshold of 1000 cps/ml provides both high specificity and sensitivity for PTC detection.

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia.

Background: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

Myocardial Steatosis Among Antiretroviral Therapy-Treated People With Human Immunodeficiency Virus Participating in the REPRIEVE Trial.

Background: People with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants.

Possible Prognostic Value of Serial Brain MRIs in Powassan Virus Encephalitis.

Powassan virus (POWV) encephalitis is a rare tickborne illness. We describe the clinical course, laboratory findings, and imaging for a patient with POWV in Massachusetts, USA. Clinical presentation and laboratory findings were nonspecific.

The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies.

Background: HIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized.

Methods: Posttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks.

HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers.

HIV posttreatment controllers (PTCs) represent a natural model of sustained HIV remission, but they are rare and little is known about their viral reservoir. We obtained 1,450 proviral sequences after near-full-length amplification for 10 PTCs and 16 posttreatment noncontrollers (NCs). Before treatment interruption, the median intact and total reservoir size in PTCs was 7-fold lower than in NCs, but the proportion of intact, defective, and total clonally expanded proviral genomes was not significantly different between the 2 groups.

Effect of Short-Term Antiretroviral Therapy Interruption on Levels of Integrated HIV DNA.

Analytic treatment interruption (ATI) studies are required to evaluate strategies aimed at achieving ART-free HIV remission, but the impact of ATI on the viral reservoir remains unclear. We validated a DNA size selection-based assay for measuring levels of integrated HIV DNA and applied it to assess the effects of short-term ATI on the HIV reservoir. Samples from participants from four AIDS Clinical Trials Group ATI studies were assayed for integrated HIV DNA levels.

Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living With HIV With Opioid Use Disorders Transitioning to the Community: Results of a Double-Blind, Placebo-Controlled Randomized Trial.

Objective: To determine whether extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among prisoners or jail detainees with HIV and opioid use disorder (OUD) transitioning to the community.

Design: A 4-site, prospective randomized double-blind, placebo-controlled trial was conducted among prison and jail inmates with HIV and OUD transitioning to the community from September 2010 through March 2016.

Methods: Eligible participants (N = 93) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 66) or placebo (n = 27) starting at release and observed for 6 months.

Treatment Trends and Outcomes in Healthcare-Associated Pneumonia.

Background: The American Thoracic Society and Infectious Diseases Society of America guidelines for management of healthcare-associated pneumonia (HCAP), first published in 2005, have been controversial regarding the selection of empiric broad-spectrum antibiotics, whether the criteria for HCAP predicts the likelihood of infection with multidrug resistant organisms, and whether HCAP patients have improved outcomes when treated with empiric broad-spectrum antibiotics.

Methods: A retrospective cohort study at 488 US hospitals from July 2007 to November 2011. Patients who met criteria for HCAP were included.

Association Between Initial Route of Fluoroquinolone Administration and Outcomes in Patients Hospitalized for Community-acquired Pneumonia.

Background: Fluoroquinolones have equivalent oral and intravenous bioavailability, but hospitalized patients with community-acquired pneumonia (CAP) generally are treated intravenously. Our objectives were to compare outcomes of hospitalized CAP patients initially receiving intravenous vs oral respiratory fluoroquinolones.

Methods: This was a retrospective cohort study utilizing data from 340 hospitals involving CAP patients admitted to a non-intensive care unit (ICU) setting from 2007 to 2010, who received intravenous or oral levofloxacin or moxifloxacin.

Investigation of Efavirenz Discontinuation in Multi-ethnic Populations of HIV-positive Individuals by Genetic Analysis.

Background: Efavirenz (EFV) based antiretroviral therapy is expanding worldwide. However discontinuation of EFV containing regimens is common in some patients, particularly black patients, due most often to neuropsychiatric side effects. These adverse drug effects often result in premature drug discontinuation, as well as considerable morbidity.

Association of guideline-based antimicrobial therapy and outcomes in healthcare-associated pneumonia.

Objectives: Guidelines for treatment of healthcare-associated pneumonia (HCAP) recommend empirical therapy with broad-spectrum antimicrobials. Our objective was to examine the association between guideline-based therapy (GBT) and outcomes for patients with HCAP.

Patients And Methods: We conducted a pharmacoepidemiological cohort study at 346 US hospitals.

Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults Previously Vaccinated With Pneumococcal Polysaccharide Vaccine.

Background: Persons with human immunodeficiency virus (HIV) infection are at increased risk of pneumococcal disease. We evaluated the safety and immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) in this population.

Methods: HIV-infected persons ≥ 18 years of age who were previously vaccinated with ≥ 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and had CD4 cell counts ≥ 200 cells/mm(3) and HIV viral loads <50 000 copies/mL were enrolled in this 3-dose PCV13 open-label study.

Design and methods of a double blind randomized placebo-controlled trial of extended-release naltrexone for HIV-infected, opioid dependent prisoners and jail detainees who are transitioning to the community.

Background: People with opioid dependence and HIV are concentrated within criminal justice settings (CJS). Upon release, however, drug relapse is common and contributes to poor HIV treatment outcomes, increased HIV transmission risk, reincarceration and mortality. Extended-release naltrexone (XR-NTX) is an evidence-based treatment for opioid dependence, yet is not routinely available for CJS populations.

Outcomes of patients with healthcare-associated pneumonia: worse disease or sicker patients?

Background: Healthcare-associated pneumonia (HCAP) is an entity distinct from community-acquired pneumonia (CAP). HCAP has a higher case-fatality rate, due either to HCAP organisms or to the health status of HCAP patients. The contribution of HCAP criteria to case-fatality rate is unknown.

An evaluation of hepatic enzyme elevations among HIV-infected released prisoners enrolled in two randomized placebo-controlled trials of extended release naltrexone.

Extended-release naltrexone (XR-NTX), an approved treatment for opioid or alcohol dependence, is a once-monthly injectable formulation of naltrexone. Hepatotoxicity concerns have limited its use, necessitating further investigation. This study aims to examine hepatic enzyme levels in participants of 2 randomized placebo-controlled trials (RCTs) of XR-NTX.

Using highly detailed administrative data to predict pneumonia mortality.

Background: Mortality prediction models generally require clinical data or are derived from information coded at discharge, limiting adjustment for presenting severity of illness in observational studies using administrative data.

Objectives: To develop and validate a mortality prediction model using administrative data available in the first 2 hospital days.

Research Design: After dividing the dataset into derivation and validation sets, we created a hierarchical generalized linear mortality model that included patient demographics, comorbidities, medications, therapies, and diagnostic tests administered in the first 2 hospital days.

Toxoplasma encephalitis in an HIV-infected patient on highly active antiretroviral therapy despite sustained immune response.

Toxoplasma encephalitis (TE) is usually diagnosed in advanced stages of HIV infection when the CD4+ count is <100-200 cells/µl. A 55-year-old woman with HIV/AIDS, well controlled on antiretroviral therapy (ART), CD4+ count in the 300 cells/μl range for >1 year presented with acute onset of headache, nausea and vomiting. She had been on her current ART regimen consisting of raltegravir, co-formulated emtricitabine/tenofovir and etravirine for three years and had been off Pneumocystis prophylaxis for 10 months (trimethoprim-sulfamethoxazole).

Successful kidney transplantation from a hepatitis B surface antigen-positive donor to an antigen-negative recipient using a novel vaccination regimen.

Transplanting a kidney from a hepatitis B surface antigen (HBsAg)-positive donor to an HBsAg-negative recipient who is naturally immune has been successful in countries endemic for hepatitis B virus (HBV). However, in most of these cases, the donors were deceased. We present a report of a successful HBsAg-discordant kidney transplantation in the United States; in this case, a living donor kidney was transplanted to a vaccinated recipient.

Genome sequence of Listeria monocytogenes 07PF0776, a cardiotropic serovar 4b strain.

Listeria monocytogenes is a food-borne bacterial pathogen commonly associated with serious invasive infections of the central nervous system or of the developing fetus. We present the genome sequence of Listeria monocytogenes 07PF0776, a serovar 4b isolate from a human myocardial abscess that exhibits enhanced invasion of cardiac tissue.