EquiPrEP: An implementation science protocol for promoting equitable access and uptake of long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP).

BACKGROUND: Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) was approved by the U.S. Food and Drug Administration in December 2021. This initial phase of implementation represents a prime opportunity to ensure equitable LAI-PrEP provision to communities often underrepresented in PrEP care before disparities in access and uptake emerge. Herein, we describe the EquiPrEP Project which utilizes an equity-oriented implementation science framework to optimize LAI-PrEP rollout in an urban safety-net clinic in New York City. METHODS: The primary objectives of this project are to: (1) increase LAI-PrEP initiation overall; (2) increase uptake among groups disproportionately impacted by the HIV epidemic; (3) preserve high PrEP retention while expanding use; and (4) identify barriers and facilitators to LAI-PrEP use. EquiPrEP will enroll 210 PrEP-eligible participants into LAI-PrEP care with planned follow-up for one year. We will recruit from the following priority populations: Black and/or Latine men who have sex with men, Black and/or Latine cisgender women, and transgender women and nonbinary individuals. To evaluate implementation of LAI-PrEP, we will utilize equity-focused iterations of the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework and the Consolidated Framework for Implementation Research (CFIR), in addition to longitudinal surveys and qualitative interviews. DISCUSSION: Novel LAI-PrEP formulations carry tremendous potential to revolutionize the field of HIV prevention. Implementation strategies rooted in equity are needed to ensure that marginalized populations have access to LAI-PrEP and to address the structural factors that hinder initiation and retention in care.

Successful Integration of HIV PrEP in Primary Care and Women's Health Clinical Practice: A Model for Implementation.

Ending the HIV Epidemic is contingent upon the increased utilization of pre-exposure prophylaxis (PrEP). The majority of PrEP in the United States is prescribed in specialty care settings; however, to achieve national implementation goals, it is necessary to expand PrEP services in primary care and women's health clinics. To this end, a prospective cohort study was conducted of health care providers participating in one of three rounds of a virtual program aimed at increasing the number of PrEP prescribers in primary care and women's health clinics within the NYC Health and Hospitals network, the public healthcare system of New York City. Provider prescribing behavior was compared at pre-intervention (August 2018-September 2019) and post-intervention (October 2019-February 2021). Among 104 providers, the number prescribing PrEP increased from 12 (11.5%) to 51 (49%) and the number of individual patients on PrEP increased from 19 to 128. The program utilized clinical integration models centering on existing STI management workflows and was associated with increased numbers of PrEP prescribers and volume of prescriptions in primary care and women's health clinics. The dissemination of similar programs could support national scale-up of PrEP.

HIV Diagnosis and the Clinical Course of COVID-19 Among Patients Seeking Care Within the New York City Public Hospital System During the Initial Pandemic Peak.

Reports conflict on how HIV infection influences the clinical course of COVID-19. The New York City (NYC) public hospital system provides care for over 14,000 people with HIV, was central in responding to the COVID-19 pandemic, and is therefore in a unique position to evaluate the intersection of these concurrent infections. Retrospective chart review of patients presenting to NYC Health and Hospitals (NYC H+H) diagnosed with COVID-19 infection from March 1, 2020, through April 28, 2020, compared people living with HIV (PLWH) and a propensity-matched (PM) control group of patients without HIV to evaluate associations between HIV status and COVID-19 outcomes. Two hundred thirty-four PLWH presented for COVID-19 testing and 110 (47%) were diagnosed with COVID-19. Among 17,413 patients with COVID-19 and without HIV, 1:n nearest neighbor propensity score matching identified 194 patients matched on age, sex, race, and any comorbidity. In the sample with COVID-19 (N = 304), PLWH (9.1%) had lower rates of mortality than controls [19.1%; PM odds ratio (PM-OR): 0.41, 95% confidence interval (CI): 0.19-0.86]. Among hospitalized COVID-19 patients (N = 179), HIV infection was associated with lower rates of mechanical ventilation (PM-OR: 0.31, 95% CI: 0.11-0.84) and mortality (PM-OR: 0.40, 95% CI: 0. 17-0.95). In the extended pandemic period through April 2021, aggregate data by HIV status suggested elevated hospitalization and mortality rates in PLWH versus people without HIV. These results suggest that the direct biological impacts of the HIV virus do not negatively influence COVID-19-related outcomes when controlling for comorbidity and demographic variables.

Tocilizumab for Severe and Critical COVID-19 Pneumonia in Queens, NYC.

New York City was hard hit by COVID-19. Elmhurst Hospital is a public hospital in Queens where more than 1500 patients were hospitalized with COVID. During the pandemic, various treatments were used with hopes of reducing the need for mechanical ventilation and death. METHODS: We retrospectively reviewed charts of patients admitted from March 25 to April 3 with severe or critical COVID-19 pneumonia who received tocilizumab compared with a similar cohort who did not. Analyses were performed to determine differences in outcomes. RESULTS: There was no observed difference in need for mechanical ventilation, length of stay, or mortality rate. In the tocilizumab-treated group, mechanical ventilation rate was 55%, and 49% of patients died. In the control group, 54% required mechanical ventilation and 46% died. Tocilizumab was overall well tolerated, although alanine aminotransferase elevation was more common in the tocilizumab-treated group. CONCLUSIONS: Tocilizumab failed to show short-term benefits in clinical outcomes in patients with hypoxic COVID pneumonia at our institution.

Treatment patterns in US patients hospitalized with COVID-19 and pulmonary involvement.

This study describes the baseline characteristics and treatment patterns of US patients hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) and pulmonary involvement. Patients hospitalized with pulmonary involvement due to COVID-19 (first hospitalization) were identified in the IBM Explorys® electronic health records database. Demographics, baseline clinical characteristics, and in-hospital medications were assessed. For evaluation of in-hospital medications, results were stratified by race, geographic region, age, and month of admission. Of 6564 hospitalized patients with COVID-19-related pulmonary involvement, 50.4% were male, and mean (SD) age was 62.6 (16.4) years; 75.2% and 23.6% of patients were from the South and Midwest, respectively, and 50.2% of patients were African American. Compared with African American patients, a numerically higher proportion of White patients received dexamethasone (19.7% vs. 31.8%, respectively), nonsteroidal anti-inflammatory drugs (NSAIDs; 27.1% vs. 34.9%), bronchodilators (19.8% vs. 29.5%), and remdesivir (9.3% vs. 21.0%). Numerically higher proportions of White patients than African American patients received select medications in the South but not in the Midwest. Compared with patients in the South, a numerically higher proportion of patients in the Midwest received dexamethasone (20.1% vs. 34.5%, respectively), NSAIDs (19.6% vs. 55.7%), bronchodilators (15.9% vs. 41.3%), and remdesivir (10.6% vs. 23.1%). Inpatient use of hydroxychloroquine decreased over time, whereas the use of dexamethasone and remdesivir increased over time. Among US patients predominantly from the South and Midwest hospitalized with COVID-19 and pulmonary involvement, differences were seen in medication use between different races, geographic regions, and months of hospitalization.

Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia.

BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).

Feasibility of Implementing Long-Acting Injectable Antiretroviral Therapy to Treat HIV: A Survey of Health Providers from the 13 Countries Participating in the ATLAS-2M Trial.

Long-acting (LA) injectable antiretroviral therapy (ART) was found noninferior to daily oral ART in Phase 3 trials with high patient satisfaction. Limited information on provider experiences with LA ART exists, which is critical to inform real-world implementation. An online survey of health providers from the 13 countries participating in the Phase 3b ATLAS-2M trial was conducted. A total of 293 providers responded to questions on LA ART feasibility. Multivariable regression was utilized to identify factors related to the feasibility of LA ART every month and every 2 months within routine care such as the characteristics, experiences, and attitudes of providers, and perceptions of patient benefits and barriers. A majority of providers indicated that it would be very feasible (62.8%) or somewhat feasible (32.1%) to administer monthly LA ART. Feasibility scores were higher for delivering LA ART every 2 months versus monthly (mean 28.3 vs. 26.9; p value <.001). African providers had higher odds of perceived overall feasibility of monthly LA ART [adjusted odds ratio (aOR) 2.9, 95% confidence interval (CI) 1.9-4.4] versus those from other regions, as did providers reporting a greater number of benefits for patients (aOR 1.1, 95% CI 1.0-1.1) versus those reporting less. Providers reporting a greater number of patient barriers to adhere to clinic appointments had lower odds of perceived feasibility of monthly LA ART (aOR 0.8, 95% CI 0.7-1.0) versus those reporting less. Findings highlight the need for further implementation research regarding barriers, facilitators, and strategies to optimize the introduction of LA ART outside of clinical trials.

A mobile health intervention in HIV primary care: supporting patients at risk for ART non-adherence.

Mobile health (mHealth) interventions that are integrated in HIV clinical settings to facilitate ongoing patient-provider communication between primary care visits are garnering evidence for their potential in improving HIV outcomes. Rango is an mHealth intervention to support engagement in HIV care and treatment adherence. This study used a single-arm prospective design with baseline and 6-month assessments for pre-post comparisons, as well as a matched patient sample for between-group comparisons to test Rango's preliminary efficacy in increasing viral suppression. The Rango sample (n = 406) was predominantly 50 years of age or older (63%; M = 50.67; SD = 10.97, 23-82), Black/African-American (44%) or Hispanic/Latinx (38%), and male (59%). At baseline, 18% reported missing at least one dose of ART in the prior three days and chart reviews of recent VL showed that nearly 82% of participants were virally suppressed. Overall 95% of the patients enrolled in Rango returned for a medical follow-up visit. Of the 65 unsuppressed patients at baseline who returned for a medical visit, 38 (59%) achieved viral suppression and only 5% of the suppressed group at baseline had an increase in viral load at 6 months despite being at risk for ART non-adherence. While viral suppression was similar between Rango participants and patients receiving treatment as usual over the same time period, it is unknown whether those patients were similarly at risk for non-adherence. Our findings support efforts to formally test this innovative approach in addressing ART non-adherence and viral suppression particularly to reach HIV treatment goals.

Prolonged QTc in HIV-Infected Patients: A Need for Routine ECG Screening.

BACKGROUND: With HIV-infected patients living longer, there is an increased burden of comorbidities related to aging, HIV itself, and polypharmacy. Cardiac morbidity is of particular importance. METHODS: This 2-group comparison study (156 HIV-positive and 105 HIV-negative patients) investigated the prevalence of abnormalities in and factors associated with an electrocardiogram (ECG) measure, corrected QT interval (QTc), where prolongation can lead to arrhythmia and sudden death. Medications prescribed (antiretroviral therapy, psychiatric medications, methadone, and antibiotics) at the time of ECG were noted. Patient characteristics, medications, QTc, and ECG characteristics were compared between the 2 groups. RESULTS: Prolongation (29% versus 19%) and extreme prolongation (6% versus 1%) in QTc were more frequent in those with HIV. Antiretroviral therapy was associated with lower odds of prolonged QTc (odds ratio [OR] = 0.35; P = .04), while methadone with higher odds (OR = 4.6; P = .01) in HIV-positive patients. With methadone and medication groups adjusted, HIV status was still associated with 17-millisecond longer QTc ( P = .04). CONCLUSION: This study provides evidence that patients with HIV may have clinically relevant longer QTc interval on ECG. Baseline and routine ECG monitoring may be warranted among patients living with HIV in clinical practice based on cumulative evidence.

Anti-α4ß7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals.

Gut homing CD4+ T cells expressing the integrin α4ß7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-α4ß7 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-α4ß7 treatment. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4ß7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for maintaining viral reservoirs, their attrition by anti-α4ß7 therapy has important implications for HIV-1 therapeutics and eradication efforts and defines a rational basis for the use of anti-α4ß7 therapy in HIV-1 infection.

Aging with HIV in the ART era.

In the current era of therapy for human immunodeficiency virus (HIV), life expectancy for persons living with HIV (PLWH) approaches that of the general population. This newly prolonged survival among PLWH is associated with an increased prevalence of comorbidities due to the inflammation, immune activation and immune senescence associated with HIV infection. Higher prevalence of tobacco and alcohol use, co-infection with viral hepatitis and traditional cardiovascular risk factors such as hypertension and hyperlipidemia contribute as well. In this review, we hope to describe the current comorbidities occurring among PLWH and bring increased awareness for conditions that may otherwise not be considered given the younger age at time of presentation.

Atherosclerotic Cardiovascular Disease and Anti-Retroviral Therapy.

In the current era of available therapy for human immunodeficiency virus (HIV), life expectancy for persons living with HIV (PLWH) nears that of the general population. Atherosclerotic cardiovascular disease (ASCVD) has become a particular burden for PLWH and society at large. PLWH have historically been shown to have an excess of cardiovascular risk and subsequent events when compared to the general population. Potential explanations include the increased prevalence of traditional risk factors, direct inflammatory and immunological effects from the HIV virus itself, and metabolic adverse effects of anti-retroviral therapy (ART). Over the past few years, there has been building evidence that chronic inflammation and immune activation independent of virologic suppression contribute significantly to excess ASCVD risk. Although independent agents and combination therapies have varying metabolic effects, the evidence from major randomized controlled trials (RCTs) supports the benefits of early initiation of ART. In this review, we will discuss the epidemiology of ASCVD in HIV-infected patients compared with the general population, give an overview of potential pathogenesis of high-risk plaque in HIV-infected patients, discuss different metabolic effects of individual anti-retrovirals, and discuss the limitations in current screening models for assessing cardiovascular disease (CVD) risk and future directions for treatment.

Acute HCV in HIV-infected MSM: modes of acquisition, liver fibrosis, and treatment.

Hepatitis C virus (HCV) is not considered to be efficiently transmitted sexually, but since the early 2000s, HCV infection of HIV-infected men who have sex with men has emerged as an epidemic worldwide. In this review, we discuss the epidemiology of sexually transmitted acute HCV, the growing body of literature regarding risk factors for acquisition, and possible mechanisms of transmission. We also discuss the progression of liver disease in these men and the advances in therapy of acute HCV with interferon-free regimens and put forth our current approach of evaluating and treating these men in New York City.

No-show to primary care appointments: why patients do not come.

BACKGROUND: Missed primary care appointments lead to poor disease control and later presentation to care. No-show rates are higher in clinics caring for underserved populations and may contribute to poorer health outcomes in this group. The objective of this study was to determine who were the patients not showing to primary care appointments and their reasons to no-show. METHODS: A retrospective study was conducted at a community health center serving a predominantly Latino, immigrant, low-income population. Adult patients >18 years old who did not show to primary care appointments during a 5-month period were called by a bilingual (English and Spanish) patient service coordinator. The patients' reported reason for missing the appointment was documented. Two-sided t test of proportions was used to compare demographic characteristics of the patients that showed to their appointments to patients that did not. RESULTS: Of 7508 scheduled appointments, 5604 were included in the analysis and 927 (16.5%) no-showed. There were 735 (79%) calls made to the patients who missed their appointments and 273 (37%) were reached. The 2 most common reasons for missing an appointment were forgetting (n = 97, 35.5%) and miscommunication (n = 86, 31.5%). When compared with patients who came to their appointments, patients who no-showed were younger (P < .0001), more likely to be black (P = .0423) or Hispanic (P = .0001), and to have Medicaid (P < .0001). CONCLUSIONS: No-show rates interfere with quality primary care. Interventions designed to target reasons for no-show are needed to help reduce the no-show rate, improve access and decrease health disparities in underserved patient populations.