Donor-Derived Tuberculosis in 3 Solid Organ Transplant Recipients From the Same Donor.

Donor-derived tuberculosis is a rare complication following solid organ transplantation, and tuberculosis screening is not a current transplant prerequisite for most donors. Donor-derived tuberculosis usually presents sooner than reactivation tuberculosis, and the most common finding is fever. We present 3 cases of donor-derived tuberculosis in the recipients of 2 kidneys and 1 liver from the same donor, who presented with unexplained fevers occurring 4-5 weeks after transplantation.

Long-acting Injectable Containing Lopinavir Eliminates Reliance on Ritonavir Pharmacokinetic Enhancement.

High-extraction protease inhibitors (e.g., for HIV and COVID-19) typically require ritonavir to enhance bioavailability by overcoming first-pass metabolism.

Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies.

Monoclonal antibodies have potential as rapidly developable agents for treatment and prevention of emerging viruses. The ACTIV-2 trial randomized persons with mild-moderate COVID-19 to the monoclonal antibody combination tixagevimab/cilgavimab via intramuscular injection (600 mg IM) or infusion (300 mg IV) versus placebo. We present final safety and laboratory outcomes; primary outcomes were previously reported.

Acute retroviral syndrome.

Purpose Of Review: To review the most important recent literature on the definition, epidemiology, clinical presentation, pathogenesis and treatment of the acute retroviral syndrome (ARS), a constellation of nonspecific symptoms and transient illness occuring in at least 50% of persons shortly after HIV acquisition. ARS is driven by initial rapid HIV viral replication and dissemination after acquisition, followed by immune activation and massive systemic inflammation. A more detailed understanding of ARS is important for the implementation of early detection efforts, treatment and public health strategies to control HIV.

Healthcare provider perspectives on integrating HIV care into cancer centers in Malawi, South Africa, Uganda, and Zimbabwe.

Background: In East and Southern Africa, treatment of people with concomitant cancer and HIV is complicated by siloed service delivery pathways, which exacerbate barriers to care and impact clinical decision-making. Integrating HIV care into cancer treatment centers may improve service delivery and overall patient outcomes.

Methods: We administered a questionnaire to clinicians and support staff at tertiary cancer referral centers in Malawi, Zimbabwe, Uganda, and South Africa to assess level of concern about clinical management of people with HIV (PWH) and cancer, barriers to integrating HIV service delivery into cancer treatment delivery, and beliefs related to HIV, antiretroviral therapy (ART), and integrated care.

Observational study of effects of HIV acquisition and antiretroviral treatment on biomarkers of systemic immune activation.

To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants' specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery.

Association of Tecovirimat Therapy With Mpox Symptom Improvement: A Cross-sectional Study-King County, Washington, May-October 2022.

Background: Data on tecovirimat effectiveness for human mpox are limited. We conducted a retrospective cross-sectional interview-based study to identify associations between tecovirimat treatment and the mpox clinical course.

Methods: Using public health surveillance data from King County, Washington, we recruited and interviewed persons diagnosed with mpox during May-October 2022.

Protocol for evaluating mechanistic pathways associated with HIV acquisition via nested Least Absolute Shrinkage and Selective Operator analysis.

Statistical analysis to evaluate mechanistic pathways can be limited by non-causal associations as well as co-linearity of high-dimensional data. Here, we present a protocol evaluating statistical associations between multiple exposure variables (sociodemographic and behavioral), immune biomarkers, and HIV acquisition. We describe steps for study setup, combining Least Absolute Shrinkage and Selective Operator with the standard regression approach, and building nested models.

The STOP COVID 2 Study: Fluvoxamine vs Placebo for Outpatients With Symptomatic COVID-19, a Fully Remote Randomized Controlled Trial.

Background: Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days.

Observational study of effects of HIV Acquisition and Antiretroviral Treatment on Biomarkers of Systemic Immune Activation.

Objective: Assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women.

Design: A retrospective study comparing inflammatory biomarkers in participants' specimens collected before and after ≥2 years of effective ART.

Methods: Inflammatory biomarkers were measured in four longitudinally collected plasma specimens, including two plasma specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression.

Safety and Efficacy of Combined Tixagevimab and Cilgavimab Administered Intramuscularly or Intravenously in Nonhospitalized Patients With COVID-19: 2 Randomized Clinical Trials.

Importance: Development of effective, scalable therapeutics for SARS-CoV-2 is a priority.

Objective: To test the efficacy of combined tixagevimab and cilgavimab monoclonal antibodies for early COVID-19 treatment.

Design, Setting, And Participants: Two phase 2 randomized blinded placebo-controlled clinical trials within the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-2/A5401 platform were performed at US ambulatory sites.

Dynamic immune markers predict HIV acquisition and augment associations with sociobehavioral factors for HIV exposure.

Prior studies attempting to link biomarkers of immune activation with risk of acquiring HIV have relied on cross sectional samples, most without proximity to HIV acquisition. We created a nested case-control study within the study in Peru, and assessed a panel of plasma immune biomarkers at enrollment and longitudinally, including within a month of diagnosis of primary HIV or matched timepoint in controls. We used machine learning to select biomarkers and sociobehavioral covariates predictive of HIV acquisition.

Racial and ethnic disparities in coronavirus disease 2019 disease incidence independent of comorbidities, among people with HIV in the United States.

Objectives: To define the incidence of clinically detected coronavirus disease 2019 (COVID-19) in people with HIV (PWH) in the United States and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19.

Design: Observational study within the CFAR Network of Integrated Clinical Systems cohort in seven cities during 2020.

Methods: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4+ cell count, and geographic area.

Long-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study.

Background: Early antiretroviral therapy (ART) initiation (ie, within 3 months of infection) limits establishment of the HIV reservoir. However, the effect of early ART initiation on the long-term dynamics of the pool of infected cells remains unclear.

Methods: In this longitudinal analysis, we included cisgender men who have sex with men (MSM) and transgender women (aged 18-54 years) at high risk for HIV infection, enrolled in the ongoing longitudinal MERLIN study in Peru between Oct 28, 2014, and Nov 8, 2018.

Factors Associated With Severity of COVID-19 Disease in a Multicenter Cohort of People With HIV in the United States, March-December 2020.

Background: Understanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies.

Setting: Centers for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care.

Methods: We identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020-December 31, 2020.

Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.

The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We posit that a priority is to develop pan-family drug cocktails to enhance potency, limit toxicity, and avoid drug resistance.

Long-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study.

Background: Early antiretroviral therapy (ART) initiation (ie, within 3 months of infection) limits establishment of the HIV reservoir. However, the effect of early ART initiation on the long-term dynamics of the pool of infected cells remains unclear.

Methods: In this longitudinal analysis, we included cisgender men who have sex with men (MSM) and transgender women (aged 18-54 years) at high risk for HIV infection, enrolled in the ongoing longitudinal MERLIN study in Peru between Oct 28, 2014, and Nov 8, 2018.