Publications by authors named "Steven Reynolds"

Globally, people with HIV (PWH) experience a broad spectrum of cognitive impairment that can be noted both before and after initiation of antiretroviral therapy (ART). Sex differences in immune function have been implicated in differential cognitive outcomes. Here, we report sex differences in cerebrospinal fluid (CSF) markers in relation to cognitive performance in a subset of ART-naïve PWH participating in the Rakai Neurology Cohort Study.

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Background: Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.

Methods: In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days.

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Article Synopsis
  • In critically ill patients, deep sedation and mechanical ventilation can lead to cognitive issues by suppressing the brain-diaphragm-lung interactions.
  • This study explored whether phrenic nerve stimulation could improve brain activity and connectivity in six patients with acute respiratory distress syndrome.
  • Results showed that phrenic stimulation, combined with mechanical ventilation, enhanced brain activity and synchronization similar to what occurs during natural diaphragmatic breathing, indicating its potential to restore important neural communication.
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Rationale: The global burden of sepsis is concentrated in sub-Saharan Africa, where inciting pathogens are diverse and HIV co-infection is a major driver of poor outcomes. Biological heterogeneity inherent to sepsis in this setting is poorly defined.

Objectives: To identify dominant pathobiological signatures of sepsis in sub-Saharan Africa and their relationship to clinical phenotypes, patient outcomes, and biological classifications of sepsis identified in high-income-countries (HICs).

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Introduction: Autoantibodies (AAbs) directed against interferon alpha (aIFNα), nuclear antigens (ANAs), anti-cardiolipin (aCL), and anti-beta 2 glycoprotein 1 (aβ2GP1), have been demonstrated to significantly correlate with the severity of acute Coronavirus Disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces these AAbs and whether they are associated with long COVID remains unclear.

Methods: The potential induction of aIFNα, ANAs, aCL, and aβ2GP1 by SARS-CoV-2 was assessed by measuring these AAbs in 224 pre- and post-infection paired serum samples from the Johns Hopkins Hospital Emergency Department (JHHED).

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Introduction: In Africa, migrants are more likely to be living with HIV and HIV viremic than non-migrants but less is known about HIV outcomes among non-migrants living in households with migrants. We compared HIV outcomes in non-migrating persons in households with and without migration.

Methods: We analyzed cross-sectional data collected between August 2016-May 2018 from non-migrating participants aged 15-49 in the Rakai Community Cohort Study in Uganda.

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Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a negative-sense RNA virus spread by Hyalomma genus ticks across Europe, Asia, and Africa. CCHF disease begins as a non-specific febrile illness which may progress into a severe hemorrhagic disease with no widely approved or highly efficacious interventions currently available. Recently, we reported a self-replicating, alphavirus-based RNA vaccine that expresses the CCHFV nucleoprotein and is protective against lethal CCHFV disease in mice.

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Background: HIV treatment programs in Africa have implemented centralized testing for routine viral load monitoring (VLM), which may result in specimen processing delays inhibiting timely return of viral load results. Decentralized, point-of-care (PoC) VLM is a promising tool for expediting HIV clinical decision-making but remains unavailable in most African settings. We qualitatively explored the perceived feasibility and appropriateness of PoC VLM to address gaps along the viral load monitoring continuum in rural Uganda.

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Article Synopsis
  • A study in Uganda from 2012 to 2019 investigated trends in HIV drug resistance during the increase of antiretroviral treatment (ART) programs, noting limited existing representative data.
  • The research found that resistance to NNRTI drugs among people starting treatment doubled over the study period, despite a decrease in overall resistance rates attributed to increased treatment access and viral suppression.
  • Key mutations contributing to this resistance were identified, with majority findings focusing on specific genetic changes, while no major mutations affecting a newer treatment drug, dolutegravir, were found.
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There is limited data on human immunodeficiency virus (HIV) evolutionary trends in African populations. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a 24-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. (p24) and (gp41) HIV data were generated from people living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994-2018) and four hyperendemic Lake Victoria fishing communities (2011-2018) under continuous surveillance.

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  • A study was conducted in a high HIV prevalence fishing community around Lake Victoria, Uganda, to analyze the impact of COVID-19 and severe flooding on HIV risk behaviors and health outcomes.
  • Data were gathered before and after these events, showing a decline in risky sexual behaviors and an increase in access to antiretroviral therapy (ART) after the COVID lockdown.
  • The results indicated that both flooding and the pandemic led to reduced transactional sex and improved ART coverage, highlighting the need for ongoing HIV management amid natural disasters and health crises.
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  • Patients with acute respiratory distress syndrome (ARDS) often suffer diaphragm dysfunction due to deep sedation and mechanical ventilation.
  • The study investigated the effects of temporary transvenous diaphragm neurostimulation (TTDN) combined with mechanical ventilation on diaphragm injury and cytokine levels in pigs with induced ARDS.
  • Results showed that TTDN significantly reduced abnormal diaphragm tissue and altered cytokine patterns compared to mechanical ventilation alone, suggesting its potential as a protective strategy in ARDS management.
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Background: The impact of migration on HIV risk among non-migrating household members is poorly understood. We measured HIV incidence among non-migrants living in households with and without migrants in Uganda.

Methods: We used four survey rounds of data collected from July 2011 to May 2018 from non-migrant participants aged 15-49 years in the Rakai Community Cohort Study.

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Context: In response to the COVID-19 pandemic, Congress passed the American Rescue Plan Act of 2021 (ARPA) that included a historic investment in the public health workforce.

Program: Charged with implementing this investment, the U.S.

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Article Synopsis
  • TLR7 is a special protein in the body that can cause a disease called systemic lupus erythematosus (SLE) when it signals too much.
  • DS-7011a is a new medicine designed to block TLR7 and was tested in a study with healthy people to see how safe it is and how well it works.
  • The study found that DS-7011a was safe, led to fewer side effects, and worked well to reduce a specific immune response, which suggests it could help treat SLE in the future.
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Objectives: Migration is associated with increased risk of HIV infection in Africa, but evidence about non-HIV sexually transmitted infection (STI) burden among African migrants is limited.

Methods: We used data from the Sexually Transmitted Infection Prevalence Study, a cross-sectional population-based study of chlamydia, gonorrhoea, trichomoniasis, syphilis and herpes simplex virus type 2 prevalence in southern Uganda, to compare STI prevalence between adults aged 18 and 49 years with and without a recent history of migration. Migration status was determined using household census data, with a recent migration history defined as having moved into one's community of current residence within the last ~18 months.

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Objectives: Public sharing of de-identified biomedical data promotes collaboration between researchers and accelerates the development of disease prevention and treatment strategies. However, open-access data sharing presents challenges to researchers who need to protect the privacy of study participants, ensure that data are used appropriately, and acknowledge the inputs of all involved researchers. This article presents an approach to data sharing which addresses the above challenges by using a publicly available dashboard with de-identified, aggregated participant data from a large HIV surveillance cohort.

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Background: Understanding of immune cell phenotypes associated with inflammatory and immunosuppressive host responses in sepsis is imprecise, particularly in low- and middle-income countries, where the global sepsis burden is concentrated. In these settings, elucidation of clinically relevant immunophenotypes is necessary to determine the relevance of emerging therapeutics and refine mechanistic investigations of sepsis immunopathology. Methods: In a prospective cohort of adults hospitalized with suspected sepsis in Uganda (N = 43; median age 46 years [IQR 36-59], 24 [55.

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Objective: Voluntary medical male circumcision (MC) is a critical tool in combination HIV prevention programmes in Africa. Self-reported MC (SrMC) status is used in HIV epidemiological surveys to assess MC coverage but is subject to response bias with limited validation. This study evaluated the utility of SrMC status as a marker of MC as well as self-reported genital lesions for genital ulcer disease (GUD) among Ugandan men.

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The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1.

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Introduction: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma associated with Plasmodium falciparum and Epstein-Barr virus, both of which affect metabolic pathways. The metabolomic patterns of BL is unknown.

Materials And Methods: We measured 627 metabolites in pre-chemotherapy treatment plasma samples from 25 male children (6-11 years) with BL and 25 cancer-free area- and age-frequency-matched male controls from the Epidemiology of Burkitt Lymphoma in East African Children and Minors study in Uganda using liquid chromatography-tandem mass spectrometry.

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Background: Empirical data on transportation access and HIV treatment outcomes in sub-Saharan Africa are rare. We assessed the association between household transport ownership and HIV viral suppression in rural Uganda.

Methods: The study was conducted among people living with HIV aged 15-49 years using cross-sectional data from the Rakai Community Cohort Study (RCCS), collected from June 14, 2018, to November 6, 2020.

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Introduction: To prioritize and tailor interventions for ending AIDS by 2030 in Africa, it is important to characterize the population groups in which HIV viraemia is concentrating.

Methods: We analysed HIV testing and viral load data collected between 2013-2019 from the open, population-based Rakai Community Cohort Study (RCCS) in Uganda, to estimate HIV seroprevalence and population viral suppression over time by gender, one-year age bands and residence in inland and fishing communities. All estimates were standardized to the underlying source population using census data.

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Background: There are limited population-level data on the pre-exposure prophylaxis (PrEP) care continuum in eastern Africa. Here, we assessed the PrEP care continuum following PrEP rollout in a Ugandan community with ~40% HIV seroprevalence.

Methods: We used cross-sectional population-based data collected between September 3 and December 19, 2018 from a Lake Victoria fishing community in southern Uganda to measure levels of self-reported PrEP knowledge, ever use, and discontinuation following 2017 PrEP rollout via a U.

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HIV incidence has been declining in Africa with scale-up of HIV interventions. However, there is limited data on HIV evolutionary trends in African populations with waning epidemics. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-five-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort.

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