Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence.

Background: Although many large, randomized controlled trials (RCT) have been conducted on antibiotic therapy for patients with primary C. difficile infections (CDI), few RCTs have been performed for patients with recurrent CDI (rCDI). In addition, fecal microbial transplant (FMT) is neither FDA-approved or guideline-recommended for patients with pauci-rCDI (first or second recurrences).

Anti-influenza hyperimmune intravenous immunoglobulin for adults with influenza A or B infection (FLU-IVIG): a double-blind, randomised, placebo-controlled trial.

Background: Since the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial.

Methods: This randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013-14 to 2017-18.

Benefit of Early versus Deferred Antiretroviral Therapy on Progression of Liver Fibrosis among People with HIV in the START Randomized Trial.

The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with human immunodeficiency virus (HIV) is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment (START) trial for liver fibrosis using the AST to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4), and assessed for a benefit of early versus delayed ART on liver fibrosis progression. ART-naïve persons with high CD4 counts (>500 cells/µL) from 222 clinical sites in 35 countries were randomized to receive ART either at study enrollment (immediate treatment arm) or when their CD4 count fell below 350 cells/µL (deferred treatment arm).

Which HIV-infected adults with high CD4 T-cell counts benefit most from immediate initiation of antiretroviral therapy? A post-hoc subgroup analysis of the START trial.

Background: Immediate initiation of antiretroviral therapy (ART) in asymptomatic adults with CD4 counts higher than 500 cells per μL, as recommended, might not always be possible in resource-limited settings. We aimed to identify subgroups of individuals who would benefit most from immediate treatment.

Methods: The START trial was a randomised controlled trial in asymptomatic, HIV-positive adults previously untreated with ART.

Comparison of the Outcomes of Individuals With Medically Attended Influenza A and B Virus Infections Enrolled in 2 International Cohort Studies Over a 6-Year Period: 2009-2015.

Background: Outcome data from prospective follow-up studies comparing infections with different influenza virus types/subtypes are limited.

Methods: Demographic, clinical characteristics and follow-up outcomes for adults with laboratory-confirmed influenza A(H1N1)pdm09, A(H3N2), or B virus infections were compared in 2 prospective cohorts enrolled globally from 2009 through 2015. Logistic regression was used to compare outcomes among influenza virus type/subtypes.

Financial Incentives for Linkage to Care and Viral Suppression Among HIV-Positive Patients: A Randomized Clinical Trial (HPTN 065).

Importance: Achieving linkage to care and viral suppression in human immunodeficiency virus (HIV)-positive patients improves their well-being and prevents new infections. Current gaps in the HIV care continuum substantially limit such benefits.

Objective: To evaluate the effectiveness of financial incentives on linkage to care and viral suppression in HIV-positive patients.

Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial.

Background: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.

Methods: The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL.

Changing Clinician Practices and Attitudes Regarding the Use of Antiretroviral Therapy for HIV Treatment and Prevention.

As part of the HPTN 065 study in the Bronx, New York and Washington, the authors, we surveyed clinicians to assess for shifts in their practices and attitudes around HIV treatment and prevention. Antiretroviral therapy (ART)-prescribing clinicians at 39 HIV care sites were offered an anonymous Web-based survey at baseline (2010-2011) and at follow-up (2013). The 165 respondents at baseline and 141 respondents at follow-up had similar characteristics-almost 60% were female, median age was 47 years, two-thirds were physicians, and nearly 80% were HIV specialists.

Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons.

Objective: Compare the effectiveness, tolerability, and safety of 3 months of weekly rifapentine and isoniazid under direct observation (3HP) versus 9 months of daily isoniazid (9H) in HIV-infected persons.

Design: Prospective, randomized, and open-label noninferiority trial.

Setting: The United States , Brazil, Spain, Peru, Canada, and Hong Kong.

Lessons learned: Infrastructure development and financial management for large, publicly funded, international trials.

Background/aims: Randomized clinical trials are widely recognized as essential to address worldwide clinical and public health research questions. However, their size and duration can overwhelm available public and private resources. To remain competitive in international research settings, advocates and practitioners of clinical trials must implement practices that reduce their cost.

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.

Background: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.

Methods: We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause.

Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

Objectives: The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/μL. We describe the demographics, HIV-specific characteristics and medical history of this cohort.

Risk assessment for healthcare workers after a sentinel case of rabies and review of the literature.

Background: After a case of rabies, healthcare workers (HCWs) had fear of contagion from the infected patient. Although transmission of rabies to HCWs has never been documented, high-risk exposures theoretically include direct contact of broken skin and/or mucosa with saliva, tears, oropharyngeal secretions, cerebrospinal fluid, and neural tissue. Urine/kidney exposure posed a concern, as our patient's renal transplant was identified as the infection source.

A large-scale, rapid public health response to rabies in an organ recipient and the previously undiagnosed organ donor.

This article describes and contrasts the public health response to two human rabies cases: one organ recipient diagnosed within days of symptom onset and the transplant donor who was diagnosed 18 months post-symptom onset. In response to an organ-transplant-related rabies case diagnosed in 2013, organ donor and recipient investigations were conducted by multiple public health agencies. Persons with potential exposure to infectious patient materials were assessed for rabies virus exposure.

When to start antiretroviral therapy: the need for an evidence base during early HIV infection.

Background: Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However, it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl.

The association between symptoms and microbiologically defined response to tuberculosis treatment.

Rationale: The lack of consistent associations between clinical outcomes and microbiological responses to therapy for some infectious diseases has raised questions about the adequacy of microbiological endpoints for tuberculosis treatment trials.

Objectives: To evaluate the association between symptoms and microbiological response to tuberculosis treatment.

Methods: We performed a retrospective analysis of four clinical trials in which participants had culture-positive tuberculosis, standardized symptom assessment, and follow-up mycobacterial cultures.

Biomarkers and bacterial pneumonia risk in patients with treated HIV infection: a case-control study.

Background: Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist.

Methods: We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial.

Progress realized: trends in HIV-1 viral load and CD4 cell count in a tertiary-care center from 1999 through 2011.

Background: HIV-1 RNA and CD4 cell counts are important parameters for HIV care. The objective of this study was to assess the overall trends in HIV-1 viral load and CD4 cell counts within our clinic.

Methods: Patients with at least one of each test performed by the Infectious Diseases Laboratory from 1999 through 2011 were included in this analysis.

Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >=300 cells/μL and HIV-1 suppression?

Among patients infected with human immunodeficiency virus (HIV), those with HIV-1 RNA <200 copies/mL and CD4 counts ≥300 cells/µL had a 97.1% probability of maintaining durable CD4 ≥200 cells/µL for 4 years. When non-HIV causes of CD4 lymphopenia were excluded, the probability rose to 99.

Current approaches to tuberculosis in the United States.

Tuberculosis is a major threat to global health, infecting a third of the world's population. In the United States, however, control of tuberculosis has been increasingly successful. Only 3.

Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study.

Background: Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals.

Three months of rifapentine and isoniazid for latent tuberculosis infection.

Background: Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion.

Methods: We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis.

Evaluating a decade of exposures to blood and body fluids in an inner-city teaching hospital.

Objective: To analyze a decade of hospital staff and student exposures to blood and body fluids (BBF) and to identify risk factors relevant to prevention strategies.

Design: Retrospective review of a 1999-2008 data set of BBF exposures. The data, maintained by occupational health staff, detailed the type of exposure, the setting in which the exposure occurred, and the occupational group of the BBF-exposed personnel.

USA300 methicillin-resistant Staphylococcus aureus bacteremia and the risk of severe sepsis: is USA300 methicillin-resistant Staphylococcus aureus associated with more severe infections?

USA300 methicillin-resistant Staphylococcus aureus (MRSA) is increasing as a cause of severe community-associated bacteremic infections. We assessed severe sepsis in response to infection in patients with USA300 MRSA compared to non-USA300 MRSA bacteremia. A cohort study was conducted from 1997 to 2008 comparing sepsis in response to infection in 271 patients with MRSA bacteremia from 4 VA hospitals.