Ryan White HIV/AIDS Part B and AIDS Drug Assistance Programs during COVID-19: safety net public health programs' challenges and innovations.

Introduction: We characterized the challenges and innovations of states' Ryan White HIV/AIDS Program (RWHAP) Part B programs, including AIDS Drug Assistance Programs (ADAPs), during the COVID-19 pandemic. In the United States, these are important safety net programs for HIV healthcare, providing essential medical and support services, and medications, to people with HIV with low incomes who are uninsured/underinsured. Methods: Data were collected via the 2021-2022 NASTAD National RWHAP Part B and ADAP Monitoring Project Report, a cross-sectional survey of state, district, and territorial programs through a mixed method study design. For quantitative data, we used descriptive statistics. Qualitative responses were coded and analyzed using content analysis. Results: Forty-seven RWHAP Part B and ADAPs responded (92% response rate). The majority of respondents reported that maintaining client eligibility (78%) and working remotely (70%) were the most challenging aspects of the pandemic, particularly in regards to implementing new telehealth and e-certification platforms. In response to COVID-19, programs introduced enrollment "grace periods" (19%), bolstered client outreach (11%), allowed more than a 30 day supply of medications (79%), and supported medication home delivery for clients (80%). Discussion: Despite the challenges of the COVID-19 pandemic, RWHAP Part B and ADAPs implemented several operational innovations in order to continue providing essential medicines and services. Other public health programs may adopt similar innovations, including digital innovations, for greater public health benefit. Future studies should assess the retention of policy innovations over time, their impact on the individual client level satisfaction or health outcomes, and what factors may improve the acceptability of telehealth and e-certification platforms.

Patient Perspective of People with HIV Who Gained Medicaid Through Medicaid Expansion: A Cross-Sectional Qualitative Study.

Given the large numbers of people with HIV (PWH) with Medicaid coverage, it is important to understand the patient experience with Medicaid. Understanding experiences with and attitudes around the program have important policy and clinical implications. The objective was to understand the patient perspective of PWH in Virginia, who transitioned to Medicaid in 2019 due to Medicaid expansion. English-speaking PWH who gained Medicaid due to Medicaid expansion in 2019 were recruited at one Virginia Ryan White HIV/AIDS Program clinic. The goal was to enroll >33% of those who newly were on Medicaid for 2019. Participants were surveyed about demographic characteristics, and semistructured interviews were performed. Descriptive analyses were performed for cohort characteristics. Using qualitative description and an open coding strategy, codebooks were generated for the interviews and themes were identified. The cohort (n = 28) met our recruitment goal. Most participants had positive feelings about Medicaid before enrollment (general: 68%; good for general health: 75%, and good for HIV care: 67%) and after enrollment (general: 93% and good for HIV care: 93%). All participants expressed incomplete understanding about Medicaid before enrollment. Seventy-nine percent needed outside help to complete enrollment. Approximately 40% described overlaps of Medicaid with other insurance/payers or gaps in insurance coverage when transitioning from one insurance/payer (such as AIDS Drug Assistance Program [ADAP] medication provision and ADAP-subsidized insurance) to Medicaid. Participants suggested more access or easier access to information about Medicaid and more explanation of Medicaid benefits would be helpful. Our findings indicate participants had mostly positive perceptions of Medicaid before and after enrollment. Even with enrollment help, participants voiced that dealing with insurance is hard. Medicaid and other programs should prioritize more access to information, smoother processes, and less burdensome enrollment/re-enrollment.

Assisters Succeed in Insurance Navigation for People Living with HIV and People at Increased Risk of HIV in a Complex Coverage Landscape.

Insurance enrollment is complex for people living with HIV (PLWH) and people at increased risk for HIV, in part, owing to needing to ensure access to adequate provider networks and appropriate formularies. Insurance for PLWH facilitates access to HIV care/treatment and, ultimately, viral suppression, which has the individual benefit of longevity and the public health benefit of decreased HIV transmission. For people at increased risk for HIV, access to insurance facilitates improved access to HIV biomedical prevention, which has the individual benefit of elimination of transmission risk and the public health benefit of decreased HIV transmission. The objective of this study was to explore perceptions of priorities related to plan navigation, barriers and facilitators for enrolling and maintaining insurance coverage, and questions related to regional, state, and federal policies impacting plans provided both on and off the Affordable Care Act (ACA) marketplace. We interviewed a national sample of assisters (n = 40), who specialize in insurance plan selection for these populations. We found that assisters tailor their approaches to HIV-specific and person-specific concerns by navigating challenges related to affordability, formularies, and provider networks. In a complex coverage landscape during a time of uncertainty about the long-term future of the ACA, assisters have mastered the ability to simplify the insurance selection process for a vulnerable population. Assisters have excelled at incorporating insurance literacy education and encouraging client engagement in the process. Assisters play an essential role in the current complicated and fragmented United States' health care delivery system for PLWH and people at increased risk for HIV and could be incorporated into the Ending the HIV Epidemic initiative.

Blocking PD1/PDL1 Interactions Together with MLN4924 Therapy is a Potential Strategy for Glioma Treatment.

OBJECTIVE: MLN4924, a pharmacological inhibitor of cullin neddylation, resulted in glioma cell apoptosis, deregulation of the S-phase of DNA synthesis and thus, offers great potential for the treatment of brain tumours. However, targeting the neddylation pathway with an MLN4924 treatment stabilized the hypoxia-inducible factor 1A (HIF1A), which is one of the main transcriptional enhancers of the immune checkpoint molecule PDL1 (programmid death ligand-1) in cancer cells. The influence of immune checkpoint molecules on glioma progression has recently been discovered; PDL1 overexpression in gliomas corresponds to a significant shortening of patient survival and a decrease of the anti-tumour immune response. We hypothesize that i) PDL1 is up-regulated in gliomas after treatment with MLN4924 and induces T-cell energy; ii) co-utilization of the PD1/PDL1 blockage with MLN4924 therapy may reduce T-cell energy and may engage MLN4924-induced tumour disruption with the immune response. METHODS: PDL1 expression and its immunosuppressive role in gliomas, glioma microenvironments, and after treatments with MLN4924 were assessed by utilizing methods of immunohistochemistry, molecular biology, and biochemistry. RESULTS: We confirmed PDL1 overexpression in clinical brain tumour samples, PDGx and established glioma cell lines, extracellular media from glioma cells, and CSF (cerebrospinal fluid) samples from tumour-bearing mice. Our primary T-cell based assays verified that the up-regulation of PDL1 in tumour cells protects gliomas from T-cell treatment and reduces T-cell activation. We found that a pharmacological inhibitor of cullin neddylation, MLN4924, exhibited strong cytotoxicity towards PDGx and established glioma cell lines, in vitro, with an IC50's range from 0.2 to 3 uM. However, we observed a significant increase of HIF1A and PDL1 in mRNA and protein levels in all glioma cell lines after treatment with MLN4924. The MLN4924-dependent induction of PDL1 in gliomas resulted in T-cell energy, which was blocked by a blockage of the PD1/PDL1 interaction. CONCLUSION: We conclude that i) PDL1 up-regulation in gliomas and the glioma microenvironment is an important chemotherapeutic target; ii) MLN4924 therapy, combined with a blockage of the PD1/PDL1 pathway, should be considered as a potential strategy for glioma treatment.