Background: This study evaluated COVID-19 risk and burden among people with HIV (PWH) in a US city with high rates of HIV and SARS-CoV-2 transmissions and examined the interrelationship between psychosocial factors and COVID-19 risk and burden. Setting: Participants were drawn from an existing consent to contact database of PWH. Database candidates were PWH, adults older than 18 years, people who had received HIV care at the University of Miami HIV clinics, people who spoke English or Spanish, and people who had agreed to be contacted for future research. Methods: An adapted version of the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study COVID-19 survey was telephonically administered, requiring 15–30 minutes. Results: Psychological stress was a predictor of COVID-19 burden (financial and social burden) and COVID-19 risk (health factors associated with an increased risk of severe health outcomes due to infection with COVID-19). Having a history of traumatic events was associated with increased COVID-19 risk, and stress was associated with increased COVID-19 burden and COVID-19 risk. Conclusions: Overall, results suggest that the intersection of the HIV and COVID-19 pandemics may be most profound among those who have experienced traumatic events; and traumatic events may be associated with heightened vigilance regarding illness and infection.

Most academic precision oncology programs have been designed to facilitate enrollment of patients in early clinical trials with matched targeted agents. Over the last decade, major changes were seen both in the targetable molecular alteration landscape and in drug development trends. In this article, we describe how the Vall d’Hebron Institute of Oncology molecular prescreening program adapted to a dynamic model of biomarker-drug codevelopment. We started with a tumor-agnostic hotspot mutation panel plus in situ hybridization and immunohistochemistry of selected markers and subsequently transitioned to tumor-specific amplicon-based next-generation sequencing (NGS) tests together with custom copy number, fusion, and outlier gene expression panels. All assays are optimized for archived formalin-fixed paraffin-embedded tumor tissues without matched germline sequencing. In parallel, biomarker-matched trials evolved from a scenario of few targets and large populations (such as PI3K inhibitors in PIK3CA mutants) to a complex situation with many targets and small populations (such as multiple targetable fusion events). Recruitment rates in clinical trials with mandatory biomarkers decreased over the last 3 years. Molecular tumor board meetings proved critical to guide oncologists on emerging biomarkers for clinical testing and interpretation of NGS results. The substantial increase of immunotherapy trials had a major impact in target prioritization and guided clinical implementation of new markers, such as tumor mutational burden, with larger exon-based NGS assays and gene expression signatures to capture microenvironment infiltration patterns. This new multiomics era of precision oncology is expected to increase the opportunities for early clinical trial matching.

The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and age macular degeneration. An mRNA microarray analysis in HIV-infected monocytes showed significant changes in the expression of several genes of this in silico derived common pathway which suggests the possible physiological relevance of this gene-circuit in driving neuroAIDS condition. Further, this unique gene network was compared with another in silico derived novel, convergent gene network which is shared by seven major neurological disorders (Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis, Age Macular Degeneration, Amyotrophic Lateral Sclerosis, Vascular Dementia, and Restless Leg Syndrome). These networks differed in their gene circuits; however, in large, they involved innate immunity signaling pathways, which suggests commonalities in the immunological basis of different neuropathogenesis. The common gene circuits reported here can provide a prospective platform to understand how gene-circuits belonging to other neuro-disorders may be convoluted during real-time neuroAIDS condition and it may elucidate the underlying–and so far unknown–genetic overlap between HIV infection and neuroAIDS risk. Also, it may lead to a new paradigm in understanding disease progression, identifying biomarkers, and developing therapies.

No abstract

Background Cryptococcal meningitis is a major cause of death among people living with HIV (PLWH). Cryptococcal antigen (CrAg) testing of asymptomatic patients is an important public health measure to reduce mortality in high incidence areas. However, limited data exists on CrAg prevalence in Central America. Methods We conducted a prospective cohort study at the two largest HIV clinics and hospitals in Honduras. CrAg in serum and cerebrospinal fluid was performed in individuals living with HIV who had CD4 ≤ 100 cells/mm 3 between 2017-2018. After CrAg testing, individuals were followed up for 12 months to assess mortality using adjusted cox proportional hazard models. Results A total of 220 PLWH were tested for CrAg of which 12.7% (n=28) tested positive. CrAg prevalence was higher among hospitalized individuals in 40% (n=10 of 25) of the cases. The proportion (35.8%) of individuals taking ART was significantly (p<0.01) lower among those who tested positive for CrAg. Overall mortality among the cohort was 11.4% (n=25 of 220) by 12 months. CrAg-positive cases were at a significantly higher risk of death [aHR: 2.69, 95%: 1.07-6.84] when compared to CrAg-negative participants. Conclusions CrAg prevalence in Honduras was high among PLWH. Moreover, individuals who tested positive for CrAg testing were at a higher risk of death. Systemic CrAg of PLWH with a CD4 ≤ 100 cells/mm 3 should be routinely performed in Central America.