Implementation of a Pharmacist-Led, Long-Acting, Injectable Cabotegravir/Rilpivirine Program for HIV-1 at Health System-Based Clinics in the New York Metropolitan Area.

Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first complete injectable antiretroviral for patients living with HIV. To facilitate patient access to long-acting injectable treatment, a system-wide, pharmacist-led, LA-CAB/RPV transition program was developed at four health system-based New York clinics. Provider referrals were received across four clinics between January 22nd, 2021, and December 31st, 2022. All referrals were evaluated by a pharmacist for clinical eligibility and medication access. The primary outcome was the treatment retention rate defined as the percentage of patients who remained on LA-CAB/RPV at 3 months post-transition. A total of 171 referrals were received, with 73 patients (43%) initiating LA-CAB/RPV. Baseline demographics included a median age of 38 years, 81% patients were male, 41% were African American, and 49% had commercial insurance coverage. The treatment retention rate was 90% at 3 months post-transition. By the end of the study period, 84% of patients who transitioned remained on LA-CAB/RPV. Treatment was discontinued due to reasons such as viral breakthrough (4%), emergence of mutations (4%), and intolerable side effects (4%). Injection site reactions were commonly reported (51%), but only resulting in treatment discontinuation for one patient. A pharmacist-led program can transition a diverse population of patients living with HIV to LA-CAB/RPV. Results from this study further add to clinical experiences with LA-CAB/RPV, demonstrating real-world treatment retention despite more frequent clinic visits for patients.

Development of a novel serological assay for the detection of mpox infection in vaccinated populations.

In 2022 the World Health Organization declared a Public Health Emergency for an outbreak of mpox, the zoonotic Orthopoxvirus (OPV) affecting at least 104 nonendemic locations worldwide. Serologic detection of mpox infection is problematic, however, due to considerable antigenic and serologic cross-reactivity among OPVs and smallpox-vaccinated individuals. In this report, we developed a high-throughput multiplex microsphere immunoassay using a combination of mpox-specific peptides and cross-reactive OPV proteins that results in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity. The New York State Non-Vaccinia Orthopoxvirus Microsphere Immunoassay is an important tool to detect subclinical mpox infection and understand the extent of mpox spread in the community through retrospective analysis.

Development of a Novel Serological Assay for the Detection of Mpox Infection in Vaccinated Populations.

In 2022 the World Health Organization declared a Public Health Emergency for an outbreak of mpox, the zoonotic Orthopoxvirus (OPV) affecting at least 103 non-endemic locations world-wide. Serologic detection of mpox infection is problematic, however, due to considerable antigenic and serologic cross-reactivity among OPVs and smallpox-vaccinated individuals. In this report, we developed a high-throughput multiplex microsphere immunoassay (MIA) using a combination of mpox-specific peptides and cross-reactive OPV proteins that results in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity. The New York State Non-Vaccinia Orthopoxvirus Microsphere Immunoassay is an important diagnostic tool to detect subclinical mpox infection and understand the extent of mpox spread in the community through retrospective analysis.

The YGetIt? Program: A Mobile Application, PEEP, and Digital Comic Intervention to Improve HIV Care Outcomes for Young Adults.

INTRODUCTION: In New York State (NYS), young adults account for the largest number of new human immunodeficiency virus (HIV) infections and struggle to seek and remain in HIV care. Digital interventions and access to peer support have demonstrated positive influences on the HIV care continuum and health outcomes. The New York State Department of Health (NYS DOH) developed YGetIt? (YGI) that combines a mobile application, GET!, peer navigation (PEEPs), and a compelling digital comic series, "Tested," to facilitate the timely entry of young people into HIV care, to prevent vulnerable youth from dropping out of care, and to achieve sustained viral load suppression among those in care. This article describes the development and early implementation of the YGI digital intervention. Intervention Design. GET! provided a high level of confidentiality and security, ease of access, and Wi-Fi accessibility. YGI enrolled 113 HIV-positive participants from a clinical setting who were individually randomized at a 1:1 ratio to receive access to GET! plus PEEPs (n = 53) or the app alone (n = 60). LESSONS LEARNED: For recruitment, staff and organization buy-in was essential to the success of the intervention, and building relationships was critical. GET! development was an iterative process. Peer Engagement Educator Professionals (PEEPs) who were tech savvy, representative of the priority population, and had shared life experience with participants were most impactful. Interest in apps declines over time and participants in the APP alone arm were less engaged. CONCLUSION: GET! is a communication and engagement tool that supports HIV care and may serve as a model for like digital interventions.

"We are Getting Those Old People Things." Polypharmacy Management and Medication Adherence Among Adult HIV Patients with Multiple Comorbidities: A Qualitative Study.

Introduction: Improvements in treatment have led to a growing population of older adults living with HIV. As this population ages, polypharmacy, or the use of more than five medications, may become more common among people living with HIV (PLWH). Methods: Two qualitative focus groups (N=7, N=8) were conducted among a sample of patients who participated in a larger study regarding differential medication adherence. Open-ended questions and probes focused on barriers and facilitators to multiple medication management as well as differential adherence. Results: Overall, patients were able to manage their polypharmacy. Social support facilitated adherence while long-term antiretroviral (ARV) use, medication-specific requirements and emotional fatigue were barriers to management. A small number of participants reported differential adherence that prioritized non-HIV medications over ARVs due to more immediate effects of non-adherence. Discussion: Findings suggest that PLWH have learned to manage their polypharmacy, but still face significant challenges adhering to multiple medications in the long-term. Future research may focus on the emotional toll of long-term ARV use and how patients' own management strategies may be leveraged to promote adherence.

Reconstruction of post-Mohs surgical wounds using a novel nanofiber matrix.

INTRODUCTION: Surgical wound healing after Mohs micrographic surgery can be challenging. Achieving an optimal aesthetic outcome is another important consideration, especially for facial lesions. OBJECTIVE: This case series evaluates the use of a novel synthetic nanofiber matrix after Mohs surgery to achieve desired results. MATERIALS AND METHODS: Four patients with NMSCs on the auricular helix underwent Mohs micrographic surgery at a single cancer center. The synthetic nanofiber matrix was applied to the prepared Mohs surgical defect and covered with a dressing. The wounds were evaluated regularly for healing progress, and an additional synthetic nanofiber matrix was applied as needed. RESULTS: Wounds were treated with an average of 1.25 applications ± 0.50 standard deviation of synthetic nanofiber matrix. The initial average wound size was 11.8 cm2. All wounds healed in 7.9 weeks ± 4.2 with excellent aesthetic results, minimal scar formation, and no skin deformity. In cases with exposed structures (cartilage and perichondrium), the synthetic nanofiber material promoted complete closure and healing. No complications were reported. Treatment using a synthetic nanofiber matrix resulted in complete wound healing in all patients. CONCLUSIONS: This study shows the synthetic nanofiber matrix is a viable option for the reconstruction of post-Mohs surgical defects.

A comparison of COVID-19 inpatients by HIV status.

COVID-19 in-hospital morbidity and mortality in people living with HIV (PLWH) were compared to HIV-negative COVID-19 patients within a New York City metropolitan health system, the hardest hit region in the United States early in the pandemic. A total of 10,202 inpatients were diagnosed with COVID-19, of which 99 were PLWH. PLWH were younger (58.3 years (SD = 12.42) versus 64.32 years (SD = 16.77), p < 0.001) and had a higher prevalence of men (73.7% versus 57.9%, p = 0.002) and Blacks (43.4% versus 21.7%, p < 0.001) than the HIV-negative population. PLWH had a higher prevalence of malignancies (18% versus 7%, p = < 0.001), chronic liver disease (12% versus 3%, p < 0.001), and end-stage renal disease (11% versus 4%, p = 0.007). Use of a ventilator, admission to the ICU, and in-hospital mortality were not different. Of the 99 PLWH, 12 were virally unsuppressed and 9 had CD4% < 14. Two of the 12 virally unsuppressed patients and 4/9 patients with CD4% < 14 died. Ninety-one of the 99 PLWH were on treatment for HIV, and 5 of the 8 not on treatment died. Among PLWH with prior values, absolute CD4 count decreased an average of 192 cells/mm3 at the time of COVID-19 diagnosis (p < 0.001). Hospitalized patients with HIV and COVID-19 coinfection did not have worse outcomes than the general population. Among PLWH, those with CD4%<14 or not on treatment for HIV had higher mortality rates. Those PLWH who received IL-6 inhibitors had lower mortality rates. PLWH given antifungal medications, hydroxychloroquine, antibiotics (including azithromycin), steroids, and vasopressors had higher mortality rates.

Structural variation of centromeric endogenous retroviruses in human populations and their impact on cutaneous T-cell lymphoma, Sézary syndrome, and HIV infection.

BACKGROUND: Human Endogenous Retroviruses type K HML-2 (HK2) are integrated into 117 or more areas of human chromosomal arms while two newly discovered HK2 proviruses, K111 and K222, spread extensively in pericentromeric regions, are the first retroviruses discovered in these areas of our genome. METHODS: We use PCR and sequencing analysis to characterize pericentromeric K111 proviruses in DNA from individuals of diverse ethnicities and patients with different diseases. RESULTS: We found that the 5' LTR-gag region of K111 proviruses is missing in certain individuals, creating pericentromeric instability. K111 deletion (-/- K111) is seen in about 15% of Caucasian, Asian, and Middle Eastern populations; it is missing in 2.36% of African individuals, suggesting that the -/- K111 genotype originated out of Africa. As we identified the -/-K111 genotype in Cutaneous T-cell lymphoma (CTCL) cell lines, we studied whether the -/-K111 genotype is associated with CTCL. We found a significant increase in the frequency of detection of the -/-K111 genotype in Caucasian patients with severe CTCL and/or Sézary syndrome (n = 35, 37.14%), compared to healthy controls (n = 160, 15.6%) [p = 0.011]. The -/-K111 genotype was also found to vary in HIV-1 infection. Although Caucasian healthy individuals have a similar frequency of detection of the -/- K111 genotype, Caucasian HIV Long-Term Non-Progressors (LTNPs) and/or elite controllers, have significantly higher detection of the -/-K111 genotype (30.55%; n = 36) than patients who rapidly progress to AIDS (8.5%; n = 47) [p = 0.0097]. CONCLUSION: Our data indicate that pericentromeric instability is associated with more severe CTCL and/or Sézary syndrome in Caucasians, and appears to allow T-cells to survive lysis by HIV infection. These findings also provide new understanding of human evolution, as the -/-K111 genotype appears to have arisen out of Africa and is distributed unevenly throughout the world, possibly affecting the severity of HIV in different geographic areas.

Psychological predictors of eating pathology in older adult women.

Eating pathology is generally considered to affect females during adolescence and early adulthood. However, in recent years, there has been an increased recognition that disordered eating occurs in middle-aged and elderly women and that the presentation is similar to that of eating disorders in younger women. In the research presented here, results of an Internet survey of older adult women (N = 245; aged 60-90 years) indicate that the factors significantly associated with eating pathology-perfectionism, depression, and sociocultural pressures to be thin-closely parallel those reported for both younger and middle-aged women.

Two Suturing Techniques for the Prevention and Treatment of Nasal Valve Collapse After Mohs Micrographic Surgery.

BACKGROUND: Tumor extirpation of nonmelanoma skin cancer (NMSC) adjacent to the alar groove, using Mohs micrographic surgery (MMS), may risk causing internal nasal valve (INV) collapse, resulting in reduced airflow during inspiration. There are many surgical options described in the literature to repair INV collapse as a postoperative corrective procedure, but few exist as an intra-operative preventative procedure. OBJECTIVE: The authors present 2 distinct methods to prevent and treat INV collapse during the repair of a perialar surgical defect caused by MMS. METHODS: A 3-point stitch method or a modified suspension suture technique was used to prevent INV collapse during the repair of MMS defects overlying the alar groove, for nonmelanoma skin cancers. The 3-point stitch was used with a complex repair. The modified suspension suture was used with flap reconstruction. RESULTS: The 3-point stitch and the modified suspension suture are simple, single-stage surgical solutions for perialar defects with collapse of the INV caused by loss of subcutaneous tissue during MMS. Once executed, patients experienced immediate subjective airflow improvement which was also supported by clinical examination. Patients were followed at 1 week and at 3 months postoperatively. Thirty-four of 35 patients reported good functional and cosmetic results and were satisfied with the final outcome. CONCLUSION: The 3-point stitch and the modified suspension suture techniques are easy and simple methods that can be incorporated into reconstruction after MMS for defects of variable depth covering any multisubunit perialar region to prevent or correct INV collapse.

Plausible Role of Acute HIV Infection Mediated Immune Activation in Causing Renal Allograft Rejection: A Case Report.

Current research states that AIDS pathogenesis has its roots in a chronic activation of immune system secondary to human immunodeficiency virus (HIV)-induced proliferation of T cells, B cells, NK cells, and macrophages. Immune activation due to acute HIV infection can be highly detrimental to allograft survival in a renal transplant recipient. In this report, we describe a 32-year-old African-American male patient who underwent a second live donor renal transplant, following which he developed acute allograft rejection coincident with newly acquired HIV seropositivity.

Religiousness and Psychological Distress in Jewish and Christian Older Adults.

OBJECTIVES: In this study, the authors explore how the association between religiousness and psychological distress varies by religious affiliation. Prior work has shown that the association between religious belief and psychological distress is stronger for Christians than Jews, while religious activity is associated with lower psychological distress for both groups. METHODS: Interviews were conducted using a community sample of 143 Christian and Jewish older adults, ages 65 and over. Quantitative measures were used to assess levels of organizational and intrinsic religiosity, as well as symptoms of depression and anxiety. RESULTS: Christians who are highly involved in the organizational aspects of their religion report fewer depressive symptoms than Jews who have high levels of organizational religiosity, and the opposite is the case at lower levels of organizational religiosity. No significant group differences were found in the relationship between religiousness and anxiety. CONCLUSIONS: The results of this study indicate a difference between Jews and Christians in the reasons that they turn to their respective religious services, particularly in late life.

Malignancies, Particularly B-Cell Lymphomas, Are a Frequent Cause of Mortality in Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy.

Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival of <2 months from time of diagnosis.

Renin modulates HIV replication in T cells.

HIV is known to subvert cellular machinery to enhance its replication. Recently, HIV has been reported to enhance TC renin expression. We hypothesized that HIV induces and maintains high renin expression to promote its own replication in TCs. Renin enhanced HIV replication in TCs in a dose-dependent manner. (P)RR-deficient TCs, as well as those lacking renin, displayed attenuated NF-κB activity and HIV replication. TCs treated with renin and Hpr displayed activation of the (P)RR-PLZF protein signaling cascade. Renin, HIV, and Hpr activated the PI3K pathway. Both renin and Hpr cleaved Agt (a renin substrate) to Ang I and also cleaved Gag polyproteins (protease substrate) to p24. Furthermore, aliskiren, a renin inhibitor, reduced renin- and Hpr-induced cleavage of Agt and Gag polyproteins. These findings indicate that renin contributes to HIV replication in TCs via the (P)RR-PLZF signaling cascade and through cleavage of the Gag polyproteins.

VDR hypermethylation and HIV-induced T cell loss.

Epigenetics contributes to the development of variety of diseases by modulation of gene expression. We evaluated the effect of HIV-induced VDR methylation on loss of TCs. HIV/TC displayed enhanced VDR-CpG methylation and increased expression of Dnmt3b but attenuated expression of VDR. A demethylating agent, AZA, inhibited this effect of HIV. HIV/TC also displayed the activation of the RAS, which was reversed by EB (a VDA). Further, HIV/TCs displayed enhanced generation of ROS and induction of DSBs but attenuated DNA repair response. However, in the presence of AZA, EB, LOS (a RAS blocker), Cat, and tempol (free radical scavengers), HIV-induced TC ROS generation and induction of DSBs were attenuated but associated with enhanced DNA repair. Additionally, AZA, EB, and LOS provided protection against HIV-induced TC apoptosis. These findings suggested that HIV-induced TC apoptosis was mediated through ROS generation in response to HIV-induced VDR methylation and associated activation of the RAS.

Assessment of the TASER XREP blunt impact and penetration injury potential using cadaveric testing.

TASER International's extended range electronic projectile (XREP) is intended to be fired from a shotgun, impact a threat, and apply remote neuromuscular incapacitation. This study investigated the corresponding potential of blunt impact injury and penetration. Forty-three XREP rounds were deployed onto two male human cadaver torsos at impact velocities between 70.6 and 95.9 m/sec (232 and 315 ft/sec). In 42 of the 43 shots fired, the XREP did not penetrate the abdominal wall, resulting in superficial wounds only. On one shot, the XREP's nose section separated prematurely in flight, resulting in penetration. No bony fractures were observed with any of the shots. The viscous criterion (VC), blunt criterion (BC), and energy density (E/A) were calculated (all nonpenetrating tests, average ± 1 standard deviation: VC: 1.14 ± 0.94 m/sec, BC: 0.77 ± 0.15, E/A: 22.6 ± 4.15 J/cm(2)) and, despite the lack of injuries, were generally found to be greater than published tolerance values.

Religiosity, authoritarianism, and attitudes toward psychotherapy in later life.

OBJECTIVE: This study explores whether intrinsic religiosity in older adults is associated with attitudes toward psychotherapy (perceived need, stigma tolerance, interpersonal openness, and confidence in mental health practitioners) when controlling for authoritarianism. METHOD: Interviews were conducted with a sample of 307 community-residing adults aged 65­82. Data were collected from 164 Black and 142 White older adults about their intrinsic religiosity, authoritarianism, and mental health help-seeking attitudes. RESULTS: Intrinsic religiosity was associated with stigma tolerance and interpersonal openness after controlling for authoritarianism. CONCLUSION: Intrinsic religiosity and authoritarianism appear to be independently related to psychotherapy attitudes. Religious older adults may prefer to seek help in religious contexts, while the association of authoritarianism to less favorable psychotherapy attitudes toward psychotherapy may be explained by a fear of external perspectives. Results on the whole reinforce the importance of including religiousness and authoritarianism in models of mental health help-seeking.