Realizing the promise of long-acting antiretroviral treatment strategies for individuals with HIV and adherence challenges: an illustrative case series.

BACKGROUND: Adherence to antiretroviral treatment (ART) remains the cornerstone of optimal HIV outcomes, including viral suppression (VS), immune recovery, and decreased transmission risk. For many people with HIV (PWH), particularly those with early-acquired HIV, structural, behavioral, and cognitive barriers to adherence and competing priorities related to life events may be difficult to overcome, resulting in nonadherence. Long-acting injectable antiretroviral therapies (LAI-ART) may be a useful strategy to overcome some of these barriers. However, to date, the approved LAI-ART strategies (e.g., cabotegravir and rilpivirine (CAB/RPV)) have targeted those who have already attained viral suppression, precluding their use in the 40% of adolescents and young adults (AYA) that VS has eluded. CASE PRESENTATION: Ms. X is a 30-year-old woman with perinatally-acquired HIV and barriers to adherence. Despite many interventions, she remained persistently viremic, with resultant immune suppression and multiple comorbid opportunistic conditions, and viral load (VL) > 10,000,000 copies/ml. Given her longstanding history of poor adherence to an oral regimen, a switch to monthly intramuscular (IM) injections and biweekly infusions of ibalizumab were initiated leading to decreased viral load to 8,110 copies/ml within two weeks. Ms. H is a 33-year-old woman with cognitive limitations due to childhood lead poisoning. Her viral load trajectory took a downward turn, precipitated by various life events, remaining elevated despite intensive case management. Initiation of LAI-ART (CAB/RPV) in this patient led to an undetectable VL (< 20 copies/ml) within two months of treatment initiation. Miss Y. is a 37-year-old woman with perinatally-acquired HIV and chronic challenges with nonadherence and longstanding immunosuppression with CD4 < 200 cells/mm3 for > 5 years. She received a 1-month oral lead-in (OLI) of cabotegravir/rilpivirine, followed by the injectable loading dose. She has since adhered to all her monthly dosing appointments, sustained VS, and transitioned to a bi-monthly injection schedule. CONCLUSION: These three individuals with HIV (perinatally and non-perinatally acquired) with longstanding nonadherence and persistent viremia were successfully initiated on LAI-ART through the process of care coordination and the collective efforts of the care team, highlighting the barriers, challenges, and the multidisciplinary coordination needed to assure successful implementation of this strategy for the most vulnerable of patients.

Ischemic Cerebroprotection Conferred by Myeloid Lineage-Restricted or Global CD39 Transgene Expression.

BACKGROUND: Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation, and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic mouse expressing human CD39 (hCD39). METHODS: A floxed-stop sequence was inserted between the promoter and the hCD39 transcriptional start site, generating a mouse in which the expression of hCD39 can be controlled tissue-specifically using Cre recombinase mice. We generated mice that express hCD39 globally or in myeloid-lineage cells only. Cerebral ischemia was induced by middle cerebral artery occlusion. Infarct volumes were quantified by MRI after 48 hours. RESULTS: Both global and transgenic hCD39- and myeloid lineage CD39-overexpressing mice (transgenic, n=9; myeloid lineage, n=6) demonstrated significantly smaller cerebral infarct volumes compared with wild-type mice. Leukocytes from ischemic and contralateral hemispheres were analyzed by flow cytometry. Although contralateral hemispheres had equal numbers of macrophages and neutrophils, ischemic hemispheres from transgenic mice had less infiltration (n=4). Transgenic mice showed less neurological deficit compared with wild-type mice (n=6). CONCLUSIONS: This is the first report of transgenic overexpression of CD39 in mice imparting a protective phenotype after stroke, with reduced leukocyte infiltration, smaller infarct volumes, and decreased neurological deficit. CD39 overexpression, either globally or in myeloid lineage cells, quenches postischemic leukosequestration and reduces stroke-induced neurological injury.

Case management in an acute-care hospital: collaborating for quality, cost-effective patient care.

Case management has recently been advanced as a valuable component in achieving quality patient care that is also cost-effective. At St. Michael's Hospital, in Toronto, Ontario, case managers from a variety of professional backgrounds are central to a new care initiative--Rapid Assessment and Planning to Inform Disposition (RAPID)--in the General Internal Medicine (GIM) Unit that is designed to improve patient care and reconcile high emergency department volumes through "smart bed spacing." Involved in both planning and RAPID, GIM's case managers are the link between patient care and utilization management. These stewards of finite resources strive to make the best use of dollars spent while maintaining a commitment to quality care. Collaborating closely with physicians and others across the hospital, GIM's case managers have been instrumental in bringing about significant improvements in care coordination, utilization management and process redesign.

Usages of Computers and Smartphones to Develop Dementia Care Education Program for Asian American Family Caregivers.

OBJECTIVES: Families of ethnic minority persons with dementia often seek help at later stages of the disease. Little is known about the effectiveness of various methods in supporting ethnic minority dementia patients' caregivers. The objective of the study was to identify smartphone and computer usage among family caregivers of dementia patients (i.e., Korean and Vietnamese Americans) to develop dementia-care education programs for them. METHODS: Participants were asked various questions related to their computer or smartphone usage in conjunction with needs-assessment interviews. Flyers were distributed at two ethnic minority community centers in Southern California. Snowball recruitment was also utilized to reach out to the families of dementia patients dwelling in the community. RESULTS: Thirty-five family caregivers, including 20 Vietnamese and 15 Korean individuals, participated in this survey. Thirty participants (30 of 35, 85.7%) were computer users. Among those, 76.7% (23 of 30) reported daily usage and 53% (16 of 30) claimed to use social media. A majority of the participants (31 of 35, 88.6%) reported that they owned smartphones. More than half of smartphone users (18 of 29, 62%) claimed to use social media applications. Many participants claimed that they could not attend in-class education due to caregiving and/or transportation issues. CONCLUSIONS: Most family caregivers of dementia patients use smartphones more often than computers, and more than half of those caregivers communicate with others through social media apps. A smartphone-app-based caregiver intervention may serve as a more effective approach compared to the conventional in-class method. Multiple modalities for the development of caregiver interventions should be considered.