Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients.

CD4 Th cells play critical roles in stimulating Ab production and in generating primary or maintaining memory CTL. The requirement for CD4 help in generating and maintaining CTL responses has been reported to vary depending on the vector or method used for immunization. In this study, we examined the requirement for CD4 T cell help in generating and maintaining CTL responses to an experimental AIDS vaccine vector based on live recombinant vesicular stomatitis virus (VSV) expressing HIV Env protein. We found that primary CD8 T cell responses and short-term memory to HIV Env and VSV nucleocapsid (VSV N) proteins were largely intact in CD4 T cell-deficient mice. These responses were efficiently recalled at 30 days postinfection by boosting with vaccinia recombinants expressing HIV Env or VSV N. However, by 60 days postinfection, the memory/recall response to VSV N was lost in CD4-deficient mice, while the recall response HIV Env was partially maintained in the same animals for at least 90 days. This result indicates that there are epitope-specific requirements for CD4 help in the maintenance of memory CD8 T cell responses. Our results also suggest that choice of epitopes might be critical in an AIDS vaccine designed to protect against disease in the context of reduced or declining CD4 T cell help.

Introduction During the early months of the COVID-19 pandemic, mortality associated with the disease declined in the United States. The standard of care for pharmacological interventions evolved during this period as new and repurposed treatments were used alone and in combination. Though these medications have been studied individually, data are limited regarding the relative impact of different medication combinations. The objectives of this study were to evaluate the association of COVID-19-related mortality and observed medication combinations and to determine whether changes in medication-related practice patterns and measured patient characteristics, alone, explain the decline in mortality seen early in the COVID-19 pandemic. Methods A retrospective cohort study was conducted at a multi-hospital healthcare system exploring the association of mortality and combinations of remdesivir, corticosteroids, anticoagulants, tocilizumab, and hydroxychloroquine. Multivariable logistic regression was used to identify predictors of mortality for both the overall population and the population stratified by intensive care and non-intensive care unit admissions. A separate model was created to control for the change in unmeasured variables over time. Results For all patients, four treatment combinations were associated with lower mortality: Anticoagulation Only (OR 0.24, p < 0.0001), Anticoagulation and Remdesivir (OR 0.25, p = 0.0031), Anticoagulation and Corticosteroids (OR 0.53, p = 0.0263), and Anticoagulation, Corticosteroids and Remdesivir (OR 0.42, p = 0.026). For non-intensive care unit patients, the same combinations were significantly associated with lower mortality. For patients admitted to the intensive care unit, Anticoagulation Only was the sole treatment category associated with decreased mortality. When adjusted for demographics, clinical characteristics, and all treatment combinations there was an absolute decrease in the mortality rate by 2.5% between early and late periods of the study. However, when including an additional control for changes in unmeasured variables overtime, the absolute mortality rate decreased by 5.4%. Conclusions This study found that anticoagulation was the most significant treatment for the reduction of COVID-related mortality. Anticoagulation Only was the sole treatment category associated with a significant decrease in mortality for both intensive care and non-intensive care patients. Treatment combinations that additionally included corticosteroids and/or remdesivir were also associated with decreased mortality, though only in the non-intensive care stratum. Further, we found that factors other than measured changes in demographics, clinical characteristics or pharmacological interventions accounted for an additional decrease in the COVID-19-related mortality rate over time.

Preserving routine primary care for people living with human immunodeficiency virus (PLWH) has been an important challenge during the COVID-19 pandemic. Telemedicine platforms have offered novel means through which care for these individuals may be maintained. Opt-In for Life is a unique mobile health application that contains telemedicine capabilities as well as other features designed specifically for the care of PLWH. Opt-In for Life was implemented early in the pandemic at Hershey Medical Center, although the center is now using a different telemedicine platform across its health care system. Institutional decisions regarding telemedicine platforms are complex. Opt-In for Life contains features that may improve the care of PLWH where telemedicine software alone may be limited.

People living with HIV (PLWH) engaged in medical care represent an accessible group to focus HIV prevention efforts. In an analysis of 1,883 PLWH from 2007 and 2015, we determined the proportion at risk of HIV transmission and identified factors associated with HIV transmission risk using multivariable mixed effects logistic regression models with random intercepts. HIV transmission risk was defined by an HIV viral load > 1,500 copies/mL and self-reported unprotected sex. We found that 174 (9.2%) individuals were at risk for HIV transmission at least once. Factors associated with HIV transmission risk included younger age (adjusted OR [95% CI] per decade decrease = 2.30 [1.84, 2.89]), illicit drug use (adjusted OR = 5.36 [3.02, 9.56]), depression (adjusted OR = 1.88 [1.10, 3.21]), and education <12th grade (adjusted OR = 2.05 [1.15, 3.67]). Thus, nearly 1 in 10 HIV-infected individuals engaged in care between 2007 and 2015 were potentially at risk of transmitting HIV. Behavioral interventions to decrease HIV transmission should focus on younger, less educated patients who are depressed and actively using illicit drugs.

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In resource-limited settings where electronic health record support is limited, such a system was feasible and appealing. In the future, this system may allow for improved HIV medication adherence tracking and be applied to medications beyond antiretrovirals.

Background Solid organ transplant (SOT) recipients are at risk of complications from COVID‐19. Nirmatrelvir/ritonavir (Paxlovid) can reduce mortality from COVID‐19 but is contraindicated in patients receiving calcineurin inhibitors (CI), which depend on cytochrome p4503A (CY3PA). In this study, we aim to show the feasibility of nirmatrelvir/ritonavir administration to SOT recipients receiving CI with coordination of medication management and limited tacrolimus trough monitoring. Methods We reviewed adult SOT recipients treated with nirmatrelvir/ritonavir from 4/14 to 11/1/2022 and assessed for changes in tacrolimus trough and serum creatinine after therapy. Results Of 47 patients identified, 28 were receiving tacrolimus and had follow‐up laboratory testing. Patients had a mean age of 55 years, 17 (61%) received a kidney transplant and 23 (82%) received three or more doses of SARS‐CoV‐2 mRNA vaccine. Patients had mild‐moderate COVID‐19 and started nirmatrelvir/ritonavir within 5 days of symptom onset. Median baseline tacrolimus trough concentration was 5.6 ng/mL (Interquartile range 5.1–6.7), while median follow‐up tacrolimus trough concentration was 7.8 ng/mL (Interquartile range 5.7–11.5, p = 0.0017). Median baseline and follow‐up serum creatinine levels were 1.21 mg/dL (Interquartile range 1.02–1.39) and 1.21 mg/dL (interquartile range 1.02–1.44, p = 0.3162), respectively. One kidney recipient had a follow up creatinine level >1.5 times baseline. No patients were hospitalized or died from COVID‐19 in the follow up period. Conclusion While administration of nirmatrelvir/ritonavir resulted in a significant increase in tacrolimus concentration, this did not result in significant nephrotoxicity. Early oral antiviral treatment in SOT recipients is feasible with medication management, even with limited tacrolimus trough monitoring.