Epigenetics, HIV, and Cardiovascular Disease Risk

Human immunodeficiency virus (HIV) is currently considered a risk factor for cardiovascular disease (CVD). With the advent of antiretroviral treatment and prevention, HIV-related morbidity and mortality rates have decreased significantly. Prolonged life expectancy heralded higher prevalence of diseases of aging, including CVD-associated morbidity and mortality, having an earlier onset in people living with HIV (PLHIV) compared to their noninfected counterparts. Several epigenetic biomarkers are now available as predictors of health and disease, with DNA methylation being one of the most widely studied. Epigenetic biomarkers are changes in gene expression without alterations to the intrinsic DNA sequence, with the potential to predict risk of future CVD, as well as the outcome and response to therapy among PLHIV. We sought to review the available literature referencing epigenetic markers to determine underlying biomechanism predisposing high-risk PLHIV to CVD, elucidating areas of possible intervention

Applying the Infectious Diseases Literature to People who Inject Drugs

People who inject drugs (PWID) presenting with injection drug use-associated infections are an understudied population excluded from most prospective infectious disease (ID) clinical trials. Careful application of the existing ID literature to PWID must consider their unique medical, psychological, and social challenges. Identification and treatment of the underlying substance use disorder are key underpinnings to any successful ID intervention

Immune Reconstitution Inflammatory Syndrome with Recurrent Paradoxical Cerebellar HIV-Associated Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML), presenting as immune reconstitution inflammatory syndrome (IRIS), is a known complication of antiretroviral therapy (ART) in people living with HIV (PLWH). Typically preceded by ART initiation, IRIS may appear simultaneously/unmasked (PML-s-IRIS) or as a delayed/worsening/paradoxical (PML-d-IRIS) presentation of known PML disease. Primary cerebellar tropism continues to be a rare presentation, and paradoxical cerebellar involvement of PML-IRIS syndrome can be a challenge for both diagnosis and management. Steroids have been suggested as a possible therapy in severe cases but the duration of steroid therapy remain elusive. Our case is that of a 34-year-old man with newly diagnosed HIV simultaneously found to have cerebellar PML. His PML lesions however worsened after initiation of ART (PML-d-IRIS) with evidence of increased intracranial pressure. Despite initial favorable response to a short duration of steroids, he had multiple recurrence of his PML lesions after steroids were discontinued. The presence of predominant cerebellar lesions and the question of how long steroids should be provided to prevent or minimize PML recurrence is the highlight of our case. This report emphasizes the need for more controlled studies to assist clinicians in the optimal diagnosis and management of PML-IRIS in PLWH

2696. Breakthrough Toxoplasmosis While on Atovaquone Prophylaxis Following Allogeneic Hematologic Stem Cell Transplantation

Abstract Background The opportunistic parasite Toxoplasma causes life-threatening complications in immunocompromised hosts such as hematopoietic cell transplantation (HCT) recipients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the agent of choice in preventing Pneumocystis jirovecii pneumonia and Toxoplasma, but bone marrow suppression often precludes its use. Broad-spectrum atovaquone also targets protozoan tachyzoite and cyst forms, but few studies examine its efficacy in prophylaxis among this vulnerable population. We present two HCT patients experiencing breakthrough toxoplasmosis despite compliance with atovaquone prophylaxis. Methods Review of literature and electronic medical records. Results Case 1. A 68-year-oldToxoplasma seropositive woman with myelodysplastic syndrome underwent Flu-Mel-ATG-matched unrelated donor HCT. On day +68 post HCT, she presented with encephalopathy. MRI brain revealed solid and ring-enhancing lesions correlating with positive CSF T. gondii PCR. Serum DNA PCR was negative. She received 12 weeks of sulfadiazine, pyrimethamine, and leucovorin with clinical and radiological improvement. Atovaquone prophylaxis was restarted given pancytopenia intolerance of TMP-SMX. Despite compliance, she experienced recurrent central nervous system toxoplasmosis. Her demise followed an unrelated ischemic cerebrovascular accident. Case 2. A 53-year-old Toxoplasma seropositive woman with CMV viremia and severe aplastic anemia limiting TMP-SMX use presented with pancytopenia on day +46 after HCT. Diagnosed with graft failure, routine screening revealed positive Toxoplasma PCR while on atovaquone prophylaxis. Toxoplasma PCR became negative after preemptive therapy. She underwent a second Flu-Cy-ATG-TBI-matched related donor HCT. 2 months later, medication noncompliance led to readmission with CMV viremia and culture-negative sepsis. Blood Toxoplasma PCR was positive at the time of death. Conclusion Toxoplasmosis prophylaxis failure can occur in allogeneic HCT recipients receiving atovaquone. When possible, TMP-SMX should remain first-line agent for this indication. In those unable to tolerate TMP-SMX, close clinical and Toxoplasma PCR monitoring may help identify reactivation and facilitate early initiation of therapy. Disclosures All authors: No reported disclosures

2667. Bridging the Gap: Sexually Transmitted Infections Testing, Treatment, and Prevention at a Miami Syringe Services Program for Women Who Inject Drugs

Abstract Background Women who inject drugs (WWID) remain understudied despite their compounded vulnerability to HIV. WWID experience increased mortality and multilevel barriers to care, including violence, homelessness, stigma, and competing priorities of childcare. In 2016, Florida passed the Infectious Disease Elimination Act (IDEA), legalizing IDEA Syringe Services Program (SSP) as the first in the state. Located in one of the country’s highest-incidence areas of HIV, IDEA SSP in Miami offers harm reduction and health opportunities outside of the traditional health care system. Previous IDEA SSP data show that WWID, representing 27% of participants overall, are more likely to report opioid injection, syringe sharing, injecting more than 5 times a day, sexual activity in the past 30 days, and transactional sex compared to their male counterparts. Methods IDEA SSP offered sexually transmitted infection (STI) testing and treatment July 1, 2022 through March 31, 2023. This descriptive study included women of childbearing age (18-44 years old) who injected drugs and were SSP participants (N=47). Results Among chlamydial infections, 2.1% had oropharyngeal, 4.3% had urethral, and 6.4% had rectal involvement. Three women (6.4%) experienced both gonococcal pharyngitis and urethritis. Rectal gonorrhea was detected in four of the 47 women (8.5%), with half testing positive twice within a 3-month period. 14 women (29.8%) demonstrated reactive syphilis testing. Of 37 women consenting to testing, three screened positive for pregnancy (8.1%). One had gonococcal pharyngitis, proctitis, and urethritis and two had other STI co-infections. Within this cohort of 47 women, 31 of the 32 HIV-negative participants initiated pre-exposure prophylaxis (PrEP) of HIV at IDEA SSP. Of the 12 with HIV, 83% reported adherence to antiretroviral therapy (ART). Three women had unknown HIV status. Conclusion Despite high HIV/STI co-infection and stigma precluding care in traditional health settings, WWID accessing IDEA SSP engaged with PrEP/ART and STI screening, including 100% of women receiving treatment for gonorrhea, chlamydia, and syphilis. Tailoring STI services at an SSP where WWID access nonjudgmental care caters to a historically neglected but key cohort in Ending the HIV Epidemic. Disclosures Hansel Tookes, III, MD, MPH, Gilead sciences: Grant/Research Support|Viiv: Grant/Research Suppor

Injection and Sexual Behavior Profiles among People Who Inject Drugs in Miami, Florida

The dynamics of injection drug use and higher-risk sexual practices compound the risk of HIV and HCV acquisition. Published literature on people who inject drugs (PWID) has examined risk of infection assuming homogeneity of cohort behavior. Categorizing subgroups by injection and sexual risk can inform a more equitable approach to how syringe services programs (SSPs) adapt harm reduction resources and implementation of evidence-based interventions. We explored injection and sexual risk profiles among PWID to determine significant predictors of class membership. Data were collected from 1,272 participants at an SSP in Miami-Dade County. Latent Class Analysis (LCA) examined how 10 injection/sexual behavior indicators cluster together to create profiles. Model fit statistics and multivariable multinomial latent class regression identified the optimal class structure and significant predictors of class membership. We assessed SSP visits, naloxone access, HIV/HCV testing and prevalence, and incidence of self-reported wounds. Three distinct profiles of injection/sexual risk were determined: Low Injection/High Sexual (LIHS) (9.4%); High Injection/Moderate Sexual (HIMS) (18.9%); and Low Injection/Low Sexual (LILS) (71.7%). Participants reporting gay/bisexual orientation and methamphetamine injection more likely belonged to the LIHS class. LIHS class members had higher prevalence of HIV, while those of HIMS reported increased hepatitis C prevalence. Compared to members of LILS, those of HIMS more likely experienced unstable housing, gay/bisexual orientation, heroin or speedball injection, and identifying as women. HIMS cohort members had more SSP visits, naloxone accessed, and higher wound incidence than those of LILS. Understanding PWID subgroups amplifies the importance of implementing evidencebased interventions such as PrEP for those engaging in highest risk behavior, with focused interventions of antiretroviral management and access to condoms for members of the LIHS class and HCV screening with wound care for those belonging to HIMS

Improving access to HIV care among people who inject drugs through tele-harm reduction: a qualitative analysis of perceived discrimination and stigma

Abstract Background Tele-harm reduction (THR) is a telehealth-enhanced, peer-led, harm reduction intervention delivered within a trusted syringe services program (SSP) venue. The primary goal of THR is to facilitate linkage to care and rapid, enduring virologic suppression among people who inject drugs (PWID) with HIV. An SSP in Miami, Florida, developed THR to circumvent pervasive stigma within the traditional healthcare system. Methods During intervention development, we conducted in-depth interviews with PWID with HIV (n = 25) to identify barriers and facilitators to care via THR. We employed a general inductive approach to transcripts guided by iterative readings of the raw data to derive the concepts, themes, and interpretations of the THR intervention. Results Of the 25 PWID interviewed, 15 were in HIV care and adherent to medication; 4 were in HIV care but non-adherent; and 6 were not in care. Themes that emerged from the qualitative analysis included the trust and confidence PWID have with SSP clinicians as opposed to professionals within the traditional healthcare system. Several barriers to treatment were reported among PWID, including perceived and actual discrimination by friends and family, negative internalized behaviors, denial of HIV status, and fear of engaging in care. Facilitators to HIV care included empathy and respect by SSP staff, flexibility of telehealth location, and an overall destigmatizing approach. Conclusion PWID identified barriers and facilitators to receipt of HIV care through the THR intervention. Interviews helped inform THR intervention development, centered on PWID in the destigmatizing environment of an SSP

Improving access to HIV care among people who inject drugs through tele-harm reduction: a qualitative analysis of perceived discrimination and stigma

Tele-harm reduction (THR) is a telehealth-enhanced, peer-led, harm reduction intervention delivered within a trusted syringe services program (SSP) venue. The primary goal of THR is to facilitate linkage to care and rapid, enduring virologic suppression among people who inject drugs (PWID) with HIV. An SSP in Miami, Florida, developed THR to circumvent pervasive stigma within the traditional healthcare system.During intervention development, we conducted in-depth interviews with PWID with HIV (n = 25) to identify barriers and facilitators to care via THR. We employed a general inductive approach to transcripts guided by iterative readings of the raw data to derive the concepts, themes, and interpretations of the THR intervention.Of the 25 PWID interviewed, 15 were in HIV care and adherent to medication; 4 were in HIV care but non-adherent; and 6 were not in care. Themes that emerged from the qualitative analysis included the trust and confidence PWID have with SSP clinicians as opposed to professionals within the traditional healthcare system. Several barriers to treatment were reported among PWID, including perceived and actual discrimination by friends and family, negative internalized behaviors, denial of HIV status, and fear of engaging in care. Facilitators to HIV care included empathy and respect by SSP staff, flexibility of telehealth location, and an overall destigmatizing approach.PWID identified barriers and facilitators to receipt of HIV care through the THR intervention. Interviews helped inform THR intervention development, centered on PWID in the destigmatizing environment of an SSP

Implementation of an integrated infectious disease and substance use disorder team for injection drug use-associated infections: a qualitative study

Hospitalizations for severe injection drug use-related infections (SIRIs) are characterized by high costs, frequent patient-directed discharge, and high readmission rates. Beyond the health system impacts, these admissions can be traumatizing to people who inject drugs (PWID), who often receive inadequate treatment for their substance use disorders (SUD). The Jackson SIRI team was developed as an integrated infectious disease/SUD treatment intervention for patients hospitalized at a public safety-net hospital in Miami, Florida in 2020. We conducted a qualitative study to identify patient- and clinician-level perceived implementation barriers and facilitators to the SIRI team intervention. Participants were patients with history of SIRIs (n = 7) and healthcare clinicians (n = 8) at one implementing hospital (Jackson Memorial Hospital). Semi-structured qualitative interviews were performed with a guide created using the Consolidated Framework for Implementation Research (CFIR). Interviews were transcribed, double coded, and categorized by study team members using CFIR constructs. Implementation barriers to the SIRI team intervention identified by participants included: (1) complexity of the SIRI team intervention; (2) lack of resources for PWID experiencing homelessness, financial insecurity, and uninsured status; (3) clinician-level stigma and lack of knowledge around addiction and medications for opioid use disorder (OUD); and (4) concerns about underinvestment in the intervention. Implementation facilitators of the intervention included: (1) a non-judgmental, harm reduction-oriented approach; (2) the team's advocacy for PWID as a means of institutional culture change; (3) provision of close post-hospital follow-up that is often inaccessible for PWID; (4) strong communication with patients and their hospital physicians; and (5) addressing diverse needs such as housing, insurance, and psychological wellbeing. Integration of infectious disease and SUD treatment is a promising approach to managing patients with SIRIs. Implementation success depends on institutional buy-in, holistic care beyond the medical domain, and an ethos rooted in harm reduction across multilevel (inner and outer) implementation contexts