Publications by authors named "David R Boulware"
Fungal infections are a major contributor to mortality for people with HIV/AIDS. Recently, researchers, clinicians, industry experts, and policymakers convened for the triennial AIDS-Related Mycoses Meeting to address critical gaps in the management of AIDS-related mycoses. Delegates highlighted several scientifically driven milestones that have significantly reduced fungal-related deaths, and the need to address outstanding challenges in diagnosis, treatment, and research.
View Article and Find Full Text PDFGlobally, 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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- A study was conducted to evaluate the effectiveness of montelukast versus a placebo in helping outpatients with mild to moderate COVID-19 recover from symptoms more quickly.
- The trial included 1,250 participants over 30 years old with confirmed COVID-19 symptoms for less than a week, who were randomly assigned to receive either montelukast or a placebo for 14 days.
- Results showed no significant difference in recovery time between the montelukast and placebo groups, with both groups having a median recovery time of 10 days and no reported deaths.
Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis; however, its clinical implications remain unclear. We analyzed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into < 100 mg/dl (72%, n = 641) and ≥ 100 mg/dl (28%, n = 249).
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- Tuberculous meningitis is a serious disease that can cause death or long-term problems for about half of the people it affects.
- Current treatment methods are based on how we treat lung tuberculosis, but they don't work as well for the brain.
- Researchers are calling for new global trials with better drugs to improve treatment and help patients with this dangerous infection.
Article Synopsis
- Despite available HIV treatments, cryptococcal meningitis still results in significant death rates, with the immune response's role in mortality remaining unclear.!* -
- A study of 337 Ugandan patients showed that higher levels of certain proinflammatory cytokines in their cerebrospinal fluid were linked to better survival rates, while lower levels of anti-inflammatory cytokines correlated with higher mortality.!* -
- The findings suggest that a stronger cytotoxic immune response in the central nervous system may enhance survival outcomes, highlighting the need for further research into immune responses for managing cryptococcal meningitis.!*
Background: In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.
Methods: We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023.
The diagnostic performance of the Visitect Advanced Disease point-of-care CD4 platform: a pragmatic mixed-methods multisite validation, costing, and qualitative analysis.
Elizabeth Nalintya Preethiya Sekar Olive L Namakula Kiiza Kandole Tadeo Richard Kwizera David R Boulware
J Acquir Immune Defic Syndr
August 2024
Article Synopsis
- The Visitect CD4 Advanced Disease test is a rapid method to assess CD4 levels in HIV patients, specifically designed to identify patients with counts above or below 200 cells/μL, and was evaluated in Uganda's semi-urban labs.
- In a study involving 1,495 blood samples, the Visitect test showed a high sensitivity of 100% but variable specificity, ranging from 63% to 99%, and a positive predictive value of 69% when compared to a confirmatory CD4 testing method.
- The findings suggest that while the Visitect test is reliable for low CD4 counts, its varying specificity needs to be taken into account based on specific clinic environments and available laboratory support for effective implementation.
Article Synopsis
- Individuals with HIV and cryptococcal antigenemia face a high risk of developing cryptococcal meningitis or death, with factors like baseline CrAg titer and CRP levels being crucial for assessing outcomes.* -
- In a study of 182 participants, those with elevated CRP levels had a higher rate of meningitis or death compared to those with normal CRP levels, specifically revealing that elevated CRP impacted low CrAg titer individuals more significantly.* -
- The research indicates a complex relationship between CrAg titers and CRP levels, suggesting that future studies should further explore this interaction to improve patient risk assessments and outcomes.*
Article Synopsis
- Mortality rates for adults with HIV-associated cryptococcal meningitis are high, between 24% and 40%, and the study explores mid-upper arm circumference (MUAC) as a modifiable risk factor for mortality.
- In a study of 433 Ugandan adults, those with a MUAC of 22 cm or less had significantly higher mortality rates, with 62% dying by the 18-week mark, indicating a strong correlation between nutritional state and survival.
- The findings suggest that MUAC can serve as an easy, bedside indicator to identify high-risk patients and pave the way for potential nutritional interventions to improve outcomes.
Article Synopsis
- Cryptococcal meningitis poses a significant risk for individuals with AIDS, and the study aims to evaluate if adding a high-dose of liposomal amphotericin B to fluconazole can reduce the incidence of meningitis among asymptomatic CrAg-positive individuals.
- In a trial with participants from Uganda, those with low plasma CrAg titers were given either liposomal amphotericin B with fluconazole or fluconazole alone for 24 weeks to assess meningitis-free survival.
- Results showed no significant difference in meningitis or death rates between the two groups, suggesting that for asymptomatic patients with low CrAg levels, adding liposomal amphotericin B does not improve outcomes and may lead to
Article Synopsis
- - Histoplasmosis is a serious fungal infection linked to high death rates in people with advanced HIV, prompting this study to assess its global prevalence of antigenuria in HIV-positive individuals.
- - The research included 15 studies after screening nearly 1,300, revealing that 11% of individuals with HIV and 13% of those with advanced HIV had detectable Histoplasma antigens in their urine.
- - The findings suggest that those with advanced HIV, especially symptomatic patients and hospitalized individuals, could greatly benefit from routine urine antigen tests for early histoplasmosis detection.
Article Synopsis
- There is currently no fast and accurate test for diagnosing tuberculous meningitis (TBM), which often delays treatment; this study aimed to create a better diagnostic tool by using a variety of data from past studies across different populations.* -
- The research involved 3,761 participants from 14 studies, identifying key predictive factors like cerebrospinal fluid glucose and HIV status, and analyzed the data using techniques like logistic regression and random forest regression.* -
- The resulting mobile app for TBM diagnosis shows promising accuracy, with further validation needed to confirm its effectiveness in diverse clinical settings.*
Article Synopsis
- This study focuses on decentralized methods for recruiting participants in a COVID-19 treatment trial, evaluating their effectiveness and efficiency.
- Five primary recruitment strategies are analyzed: search engine ads, paid ads through national and regional testing companies, electronic health record messaging, and word of mouth.
- The study compares these methods based on patient demographics, recruitment efficiency, and associated costs.
Background: Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day.
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- The study explores how HIV persists in the central nervous system (CNS) and the role of different brain regions in drug exposure, highlighting the differences between cerebrospinal fluid (CSF) and actual brain tissue.
- Researchers measured concentrations of four antiretroviral drugs in 13 CNS regions and plasma from 49 Ugandan decedents collected during autopsy, noting significant variations in drug penetration across the brain.
- Findings revealed that drug levels in the brain were generally lower than in CSF, and postmortem changes in drug concentrations were observed in a mouse model, suggesting that further investigation into these regional differences could help understand HIV compartmentalization and potential neurotoxicity.
Article Synopsis
- Recent trials have influenced guidelines for cryptococcal meningitis treatment, but the 2010 IDSA guidelines have not been updated to reflect these changes, particularly from the 2022 AMBITION-cm trial which suggests a new regimen might be effective.
- A survey conducted in June 2023 revealed that only 14% of responding physicians had used the AMBITION-cm treatment, and around 10% preferred it in hypothetical scenarios due to concerns over its applicability and lack of endorsement in existing guidelines.
- The findings indicate that while some physicians are using the new regimen, most are not, highlighting a need for further research on its effectiveness in diverse patient populations.
Article Synopsis
- Cryptococcal meningitis is a significant cause of mortality in individuals with late-stage HIV, and the relationship between cerebrospinal fluid (CSF) immune responses and leukocyte infiltration's impact on survival is being studied.
- A study involving 401 adults in Uganda showed that those with a higher CSF leukocyte count (≥50/μL) had a 68% survival rate at 18 weeks, compared to 52% for those with lower counts, indicating that immune response is critical for survival.
- Increased survival correlates with elevated levels of specific immune markers, including T helper cytokines and certain chemokines, suggesting that a robust immune response in CSF is vital for improving outcomes in patients with HIV
Article Synopsis
- - The study aimed to determine the effectiveness of montelukast, a medication, versus a placebo in helping outpatients with mild to moderate COVID-19 recover from their symptoms more quickly.
- - Conducted as part of the ACTIV-6 trial, 1250 participants aged 30 and older were enrolled from across 104 U.S. sites, receiving either montelukast or a placebo for 14 days.
- - Results showed no significant difference in recovery times between those taking montelukast and those taking the placebo, with both groups having a median recovery time of 10 days and minimal hospitalizations or adverse events reported.
Article Synopsis
- - Metformin shows antiviral properties against SARS-CoV-2 by inhibiting protein translation through the mechanistic target of rapamycin pathway, leading to significant reductions in hospitalizations, emergency visits, and long COVID risk in the COVID-OUT trial.
- - The COVID-OUT trial involved 999 participants and compared metformin, fluvoxamine, and ivermectin; it found a 3.6-fold reduction in viral load with metformin compared to placebo, and reduced rates of detectable viral load and viral rebound.
- - The results indicate that metformin effectively lowers SARS-CoV-2 viral load, potentially explaining its clinical effectiveness, while neither ivermectin nor fluvoxamine showed significant benefits over placebo.
Article Synopsis
- - The review addresses the challenges in diagnosing and treating patients with a history of cryptococcal meningitis who experience recurring symptoms after improvement, highlighting significant gaps in current medical knowledge.
- - The authors analyzed data from 28 cases of paradoxical immune reconstitution inflammatory syndrome (IRIS) and 81 cases of microbiological relapse, finding that traditional indicators like CD4 and cerebrospinal fluid white cell counts are insufficient for differentiating between these two conditions.
- - They emphasize that cryptococcal antigen tests are inadequate for distinguishing relapse from other recurrent symptoms, urging the need for newer research definitions and the development of fast, reliable diagnostic tests.
Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges.
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- Stress urinary incontinence (SUI) is a common issue in women that causes unintentional urine leakage during activities, impacting their quality of life, and current non-surgical treatments are insufficient.
- The study evaluated the effectiveness of the Flyte intra-vaginal device, which strengthens pelvic floor muscles using two forms of mechanotherapy during a 12-week pelvic floor muscle training regimen.
- Results showed significant reductions in urine leakage (measured by 24-hour pad weight) after 6 and 12 weeks, indicating the treatment's effectiveness, though the study faced limitations in statistical power due to unexpected results from the therapy.