Viral Load Research Articles

P-543. A Descriptive Report of Discontinuation Rates, Blips, and Viremia Associated with Cabotegravir/Rilpivirine at One Ryan White HIV/AIDS Program-funded site in Northern Virginia

Abstract Background Cabotegravir/rilpivirine (CAB/RPV) is the first and only long-acting complete regimen for the treatment of HIV-1 infection. Rates of discontinuation, viral blips, and viremia were low in Phase III clinical trials for CAB/RPV, but data from additional locations in real-world conditions remains lacking. This descriptive report explores the frequency of these occurrences in patients treated with CAB/RPV at one Ryan White HIV/AIDS Program (RWHAP)-funded site. Methods This was a single-center, retrospective, observational chart review of people living with HIV at one institution in Northern Virginia. Patients were included if they received at least one dose of injectable CAB/RPV between January 2021 and April 2024. Data collected from the electronic medical record included demographics, body mass index (BMI), history of antiretroviral drug mutations, HIV viral load, and HIV treatment history. Results A total of 107 patients were included in this study with a mean age of 45 years. Of these, 2% were assigned female at birth and 49% were Black. In the study period, 16% of patients discontinued the medication. The most common causes for discontinuation were adverse effects, insurance denials, patient preference for oral therapy, and frequently missing appointments. Of the 17 patients who discontinued therapy, only one was discontinued due to virologic failure. As of April 2024, 85 patients remain on CAB/RPV. Of these, 43% have experienced at least one blip, 25% have experienced low-level viremia, and 61% have experienced either a blip or low-level viremia since starting CAB/RPV. Duration of therapy ranged from 1 to 1020 days (average 579 days) since first injection and longer duration of therapy weakly correlated with prevalence of blips or viremia. 92% of doses have been administered within the allowable 14-day treatment window. There was no significant difference between BMI at the start of treatment to April 2024. Conclusion Among patients treated with CAB/RPV, viral blips and low-level viremia are common but are not associated with treatment discontinuation or treatment failure. Rates of discontinuation due to adverse effects were higher than what was observed in Phase III randomized controlled trials of CAB/RPV, though treatment failure was uncommon as expected. Disclosures All Authors: No reported disclosures

P-475. Anal Cancer Screening in HIV Positive MSM and TGW: A Multistage Quality Improvement Project

Abstract Background Men who have sex with men (MSM) and transgender women (TGW) living with HIV (PLHIV) have an estimated 37-fold increased risk of anal cancer compared to the general population. Currently there are no national guidelines on screening for anal cancer with cytological analysis creating discrepancies in anal cancer screening and increasing risk of progression to anal cancer. We reviewed the MSM and TGW PLHIV cohort in our institution to identify demographics, risk factors, and anal cancer screening rates, we also identified outcomes of patients with cytological testing. Methods We conducted a retrospective chart review of MSM PLHIV over the age of 18, who were seen in Stony Brook University HIV clinic from 02/01/21 to 02/01/24. Demographics, smoking history, HIV viral load, human papillomavirus (HPV) vaccination status, and sexually transmitted infection (STI) history was obtained from chart review and compared between patients with and without anal cancer screening with Chi square test. Results We identified a total of 160 MSM and 2 TGW. The majority of patients were unvaccinated for HPV (n=144; 88%). 84% had suppressed HIV viral load (n=137), 49% had a smoking history (n=80), and 35% had recent history of STI (n=57). Only 32% (n=53) patients had anal cancer screening done. We also found the patients who were less than 50 years, who had smoking history and recent STIs had a higher chance of being screened. Fifty-three patients were identified with prior cytological analysis, 15 (28.6%) with atypical squamous cells of unknown significance, 6 (11.3%) with low-grade, and 1 (1.9%) with high-grade squamous epithelial lesions. Conclusion We identified that anal cancer screening rates were low at our institution despite the prevalence of risk factors such as smoking, high prevalence of STIs and low HPV vaccination status. Nearly 50% of patients had abnormal cytological analysis, highlighting the importance of establishing and implementing anal cancer screening. We have implemented an institutional protocol from 03/01/24 to increase the screening rates for anal cancer for this high risk population. Disclosures All Authors: No reported disclosures

P-542. Long-Acting (LA) Intramuscular (IM) Cabotegravir and Rilpivirine (CAB/RPV) in Adults for the Maintenance of HIV-1 Suppression in County-Based Clinics in Riverside County

Abstract Background IM CAB/RPV effectively maintained HIV viral suppression in prior randomized controlled trials. The study aimed to apply CAB/RPV trial results in a county population. The secondary aim was to characterize socioeconomic factors affecting CAB/RPV implementation.Figure 1.Baseline vs. 6-Month Post CAB/RPV Viral Load and CD4(Top) HIV viral load between baseline, 3-month, 6-month, and 12-month post-CAB/RPV switch. (Bottom) CD4 count between baseline, 3-month, 6-month, and 12-month post-CAB/RPV switch Methods We conducted a retrospective cohort study including adult HIV patients virologically suppressed on oral antiretroviral and switched to CAB/RPV. Patients received at least one oral or IM CAB/RPV dose from Riverside University Health System between January 2021 to 2024. We collected data by chart review. The primary outcome was the patient percentage of HIV-1 RNA ≤ 50 copies/mL. The secondary outcomes were virologic failure, CD4 count, adverse events, and adherence. We used McNemar’s test for categorical variables and Wilcoxon Signed-Rank test or paired t-test for continuous variables to compare outcomes at baseline and 6-month post CAB/RPV switch. We used univariant analysis to evaluate risk factors for the primary outcome. We used a binary logistic regression model to evaluate risk factors for discontinuation.Table 1.Risk Factors to HIV RNA level > 50 copies/mL at 6 months*RUHS= Riverside University Health System Results We included 169 patients. 123/128 patients (96.1%) maintained HIV-1 RNA level ≤ 50 copies/mL at 6 months after CAB/RPV switch (p=0.727). CD4 count did not significantly change (p=0.115). Age, clinic type, and side effects were associated with HIV-1 RNA level > 50 copies/mL at 6 months. Virologic failure occurred in 5/128 patients (3.9%). 62/169 patients (36.7%) discontinued therapy. After controlling for demographic and clinical factors, a higher California Healthy Place Index (CA HPI), and longer distance to clinic were significant risk factors for discontinuation. There were more adverse events reported post-switch (52.7%, p< 0.001), the highest being injection site reactions (54/169, 32%). The number of rescheduled appointments was not different post-switch (70.3% vs 67.2%, p=0.683).Table 2.Binomial Logistic Regression Analysis for Therapy Discontinuation (n=197) Conclusion 96.1% of county patients maintained HIV viral suppression after CAB/RPV switch, consistent with prior trials. We observed a higher discontinuation rate compared to prior literature, associated with multiple socioeconomic factors. Resources for social and financial barriers are vital for CAB/RPV implementation to ensure treatment success and patient retention.Table 3.Baseline vs. 6-Month Post CAB/RPV Reported Adverse Reactions#Post CAB/RPV switch adverse events included all reported adverse events in patients who received at least one dose of oral or IM CAB/RPV Disclosures All Authors: No reported disclosures

P-1390. Anorectal Human Papillomavirus (HPV) Infection in HIV-Positive Men who have Sex with Men (MSM) in Nicaragua

Abstract Background HIV-positive men who have sex with men (MSM) are at increased risk for sexually transmitted infections, including anorectal HPV, with the consequent likelihood of neoplasia at that level. There is a complete lack of information on this situation in Nicaragua. This study explores and establishes for the first time the prevalence of anorectal HPV infection in HIV-positive MSM and its correlation with cytological abnormalities, and some associated behavioral, virological, and immunological factors in Nicaragua.Figure 1.Prevalence of HPV Anorectal Infection in MSM HIV Positive Diagnosed by RT-PCR Xpert HPV. Methods A prospective, multicenter cohort study was conducted between January 2023 at December 2023, at Dr. Fernando Vélez Paiz Hospital, Antonio Lenin Fonseca Hospital, and Manolo Morales Hospital in the city of Managua, Nicaragua. HIV-positive MSM patients were enrolled to the study with prior consent. Anorectal swab samples were processed by molecular method for HPV detection (GeneXpert HPV®) of different genotypes individually or grouped into genetic patterns (16, 18/45, P3: 31/32/35/52, P4: 51/59, and P5: 39/56/66/68). In addition, anorectal Pap smears were performed for cytopathology study. All samples were processed in the microbiology and pathology laboratories of the Dr. Fernando Vélez Paiz Hospital, the main center of the research.Figure 2.Different Genotypes Detected by Xpert HPV Anorectal Infection in MSM HIV Positive. Results A total of 44 patients were enrolled in the study. A significant proportion of patients declined to participate in the study. The mean age was 35.2 ± 12.4 years. Most of the patients reported having a passive or versatile sexual role. 22.7% were naïve to antiretroviral therapy (ART). The prevalence of anorectal HPV infection was 86.3% (Figure 1). The most frequent genotype was HPV 16 (21.7%) (Figure 2). In the combined genotype patterns, P3 (31/32/35/52) was observed in 40.5% of patients. All patients were infected with more than one genotype. 31.5% of those infected had cytological abnormalities, the most frequent being low-grade squamous intraepithelial lesion (Table 1). HPV-positive patients were younger, had a higher viral load, and a lower CD4+ lymphocyte count (Table 2).Table 1.Abnormalities in Anal Papanicolau in MSM HIV-positive con HPV Infection Diagnosed by Xpert HPV. Conclusion The prevalence of anorectal HPV infection in this study is high, with serotype 16 being the most frequent. Almost a third of them have altered cytology, with low-grade squamous intraepithelial lesion being the most frequent finding.Table 2.Differences in Age, HIV Viral Load and Count of Lymphocyte CD4+ in MSM HIV-Positive with and wihtout HPV Infection Disclosures All Authors: No reported disclosures

P-483. Late presentation of People Living With HIV in “Treat All” Era in Maputo City, Mozambique

Abstract Background Advanced HIV disease (AHD), defined as People Living with HIV with a CD4 cell count < 200 cells/mm3 or WHO clinical stage 3 or 4, increases the risk of severe opportunistic infections, hospitalizations, and death. Programmatic data from Mozambique showed a reduction in the prevalence of AHD at ART initiation from 73% to 37% during 2004-2014. Since 2016, Mozambique has adopted the “Treat all” strategy, and data on AHD at presentation for care is limited. We assess the prevalence of AHD in recently diagnosed HIV clients ART naïve. Relation between Age and Gender and AHD prevalece Methods An analysis of baseline data of a prospective cohort study in newly HIV-diagnosed ART naïve at Mavalane Health Centre (MHC) located in a periurban area in Maputo City. April 2021-November 2022, all HIV-1 diagnosed ART naïve above 18 years of age were enrolled. A questionnaire was administered to assess risk factors for HIV infection, and CD4+ T cell counts and HIV viral load were determined. Results A total of 1,025 PLHIV were enrolled, of whom 560 (55%) were females, median age of 35 (IQR: 30, 43) years, and mean BMI was 23.7 kg/m2 (SD: 4.48) with 8.1% under 18.5 kg/m2. The overall median CD4 + cell count was 252 (IQR: 140, 421) cells/mm3, with 46.0% (214/465, 95%CI: 41.4-50.7%) and 32.7% (183/560, 95%CI: 28.8-36.7%) of males and females, respectively, below 200 cells/mm3. There was an age-ascending trend (p-value: < 0.001) among females from 15.0% (95%CI: 8.6-23.5%) to 53.7% (95%CI: 43.2-64.0%). There was age dependency among males (p-value: 0.1887). The overall median log10 HIV-RNA was 5.12 (IQR: 4.67, 5.52), 4.41 (IQR: 3.63, 4.94) among AHD and non-AHD, respectively (p-value < 0.001). Conclusion This study unveiled a high burden of AHD, showing that even in an era when countries are working on strategies for early HIV diagnosis and treatment to reduce the incidence of HIV and mortality associated with opportunistic infections, clients are still presenting in an advanced stage of the disease. Disclosures All Authors: No reported disclosures

P-560. Evaluating the Use of Long-Acting Lenacapravir among Treatment-Experienced Adults with HIV in a Large Community-Based Clinic Network

Abstract Background Lenacapravir (LEN) is the first-in-class long-acting capsid inhibitor approved by the FDA in December 2022 for the treatment of multi-drug resistant HIV in adults. It is administered by subcutaneous injection every six months in combination with other antiretrovirals (ARV). It is indicated for heavily treatment-experienced people with HIV (PWH). We assessed the use of long-acting LEN within the CAN Community Health Network. Methods A retrospective analysis of electronic medical records within the CAN Community Health Network of 23 clinics located throughout six US states. People with HIV who received one or more injections of LEN for treatment between December 2022 and April 2024 were included. Demographic characteristics, HIV viral load, CD4 count and composition of pre-LEN ARV regimens were studied. Results Twenty-four PWH were identified as receiving one or more injections of LEN between December 2022 and April 2024. The median age was 58 years; 79% were male, 67% White and 71% Non-Hispanic (Table 1). Mean number of injections received was 2. Pre-LEN HIV VL was >50 copies/mL in 8 PWH (33%) and pre-LEN HIV VL was < 50 copies/mL in 16 PWH (67%). Five PWH (21%) had a pre-LEN CD4 count < 200 and 19 PWH (79%) had a pre-LEN CD4 count >200. Post-LEN HIV VL decreased in all eight patients with HIV VL >50 copies/mL (Table 2). Pre-LEN ARV regimens included a median of 4 active agents with 92% of them containing integrase inhibitors (INSTIs), 71% NRTIs and 58% protease inhibitors (PIs) (Table 3). Reasons for switching to a LEN-combination regimen in those with HIV VL < 50 included: simplification, side effects or intolerance to oral ARVs and non-adherence. Three (13%) patients stopped LEN due to injection site reactions (ISRs), 1 patient (4%) stopped due to side effects, 2 patients (8%) were lost to care and 1 patient (4%) was switched to an oral alternative due to travel. Conclusion The majority of PWH who were switched to LEN-combination regimens were older males with HIV VL < 50 copies/mL. Reasons for switching included simplification, side effects to other ARVs and non-adherence. Of those with HIV VL > 50 copies/mL prior to switching to a LEN-combination regimen, all had a decrease in their HIV VL. The most common reason for discontinuation was ISRs. Sample size was small and a longer duration of follow-up is needed. Disclosures Jessica A. Altamirano, MD, FIDSA, Gilead Sciences: Speaker's Bureau

P-8. Assessment of 13-valent pneumococcal conjugate vaccine effectiveness among people living with HIV in the United States

Abstract Background People living with HIV (PLWH) have increased risk of pneumococcal infections. Although pneumococcal conjugate vaccines (PCVs) have been recommended for immunocompromised (IC) people, data regarding PCV effectiveness among PLWH are limited.Table 1.Baseline characteristics prior to weighting of 350,399 PLWH by receipt of PCV13 by end of baseline, United States, 2014-2022 Methods People with an HIV diagnosis code (index) from 1/1/2014 through 12/31/2021 were identified in US administrative claims. PLWH age ≥ 18 years without prior PCV13 vaccination were followed from six months post-index (baseline period) through 9/30/2022 for first episodes of invasive pneumococcal disease (IPD), pneumococcal pneumonia (PP) due to any serotype, and all-cause pneumonia (ACP) using diagnosis codes. Marginal structural Cox models estimated hazard ratios (HR) for each outcome and inverse probability weights were used to control for confounding/dropout. Vaccine effectiveness (VE) was estimated as (1-HR) x 100%. Candidiasis, all-cause diarrhea, and accidental injury served as negative control outcomes to assess residual confounding.Table 2.PCV13 VE against IPD, PP, ACP, and negative control outcomes among 350,399 PLWH, United States, 2014 - 2022 Results 350,399 PLWH were included; 8% had received PCV13 during baseline, rising to 24% PCV13 by end of follow-up, and 25% received PPSV23. Mean follow-up was 2.9 years. Compared with PCV13-unvaccinated PLWH, greater proportions of PCV13-vaccinated PLWH were adherent to HIV medications and received CD4 tests, viral load tests, and influenza vaccination during baseline (Table 1). Overall weighted VEs (95% confidence intervals [CIs]) for IPD, PP, and ACP were 22% (5%, 36%), 17% (4%, 29%), and 8% (6%, 11%), respectively (Table 2). VE was highest for years 0 to < 3 of follow-up (0 to < 3 yr VE: 35% [13%, 51%]) for IPD, 26% [9%, 39%] for PP, and 11% [8%, 15%] for ACP) (Table 3). The negative control outcomes suggested residual confounding (Tables 2-3).Table 3.Weighted PCV13 VE against IPD, PP, ACP, and negative control outcomes among PLWH during 0 to < 3, 3 to < 5, and 5 to < 7 years of follow-up, United States, 2014 - 2022 Conclusion This study demonstrated real-world PCV13 VE against IPD and pneumonia among PLWH during the first three years of follow-up, but little evidence of VE thereafter. However, assessing VE after three years of follow-up was limited by decreased sample size and events. Overall, VE was relatively high considering pneumococcal outcomes were not specific to vaccine serotypes and ACP was not specific to pneumococcus. Residual confounding may also exist, but its direction remains unclear. Disclosures Amanda C. Miles, MPH, Pfizer: Pfizer employee|Pfizer: Pfizer employee|Pfizer: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company) Sarah J. Willis, PhD, MPH, Pfizer, Inc.: Employment|Pfizer, Inc.: Stocks/Bonds (Private Company) Erica Chilson, PharmD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds (Public Company) Lindsay Grant, PhD, MPH, Pfizer, Inc: Employee of company|Pfizer, Inc: Stocks/Bonds (Private Company) Christian Theilacker, MD, DTM&H, Pfizer Inc: I am a Pfizer Employee|Pfizer Inc: Stocks/Bonds (Public Company) Cassandra Hall-Murray, PharmD, Pfizer, Inc.: employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Qi Yan, PhD, MS, Pfizer: Pfizer employee|Pfizer: Stocks/Bonds (Public Company) Jeffrey T. Vietri, PhD, Pfizer Inc.: Employment|Pfizer Inc.: Stocks/Bonds (Public Company) Tamuno Alfred, PhD, Astellas Pharma: Astellas Pharma employee|Pfizer: Previous Pfizer employee|Pfizer: Stocks/Bonds (Public Company) Alejandro D. Cane, MD, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company) Bradford D. Gessner, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)

P-1849. Investigating the Impact of SARS-CoV-2 on the Immune Response to Other Pathogens Using VirScan Epitope Profiling

Abstract Background The emergence and rapid spread of SARS-CoV-2 since 2019 caused substantial global morbidity and mortality and continues to burden healthcare systems worldwide. Public health measures implemented to reduce SARS-CoV-2 spread also reduced circulation of other seasonal respiratory viruses, likely causing gaps in population-level immunity. Whether SARS-CoV-2 infection may dampen immune responses against other pathogens is highly debated and not well understood.Figure 1.VirScan analyses of serum samples pre- and post- clinically confirmed SARS-CoV-2 infection. (A) VirScan total epitope hits and geometric mean (gMean) of epitope binding (EB) scores for SARS-CoV-2 pre- and post- clinically confirmed SARS-CoV-2 infection. (B) gMean of EB scores for select pathogens pre- and post- clinically confirmed SARS-CoV-2 infection. Timepoints included in the VirScan analyses were between 15-174 days prior to and 31-155 days after clinically confirmed SARS-CoV-2 infection. Gray lines denote paired samples for individual subjects. Statistically significant adjusted p values of < 0.05 were determined using paired t test with Holm correction. Methods In 2022, we conducted a longitudinal study of immunocompetent adults ( > 18 years) with recent SARS-CoV-2 infection or vaccination history and increased risk of social or occupational exposure to respiratory viruses. Subjects were followed for 6 months and weekly symptom surveys, blood samples at enrollment, 3 and 6 months post-enrollment, and nasal swabs at report of symptoms were collected. Swabs were tested by RT-PCR (OpenArray) for 27 respiratory pathogens, including SARS-CoV-2. Serum antibodies were assessed by VirScan PhIP-seq for specificity to a broad library of antigen epitopes for clinically relevant pathogens, measuring total epitope hits and epitope binding (EB) scores, a measure similar to antibody titer. Results Of 43 subjects with paired serum samples > 1 week prior to and > 28 days after clinically confirmed SARS-CoV-2 infection, 32 subjects with viral load < Ct 22.2 were assessed by VirScan. SARS-CoV-2 epitope hits and EB scores were significantly increased post-infection compared to pre-infection (Fig 1A). SARS-CoV-2 infection was associated with reduced EB scores for adenovirus D and S. aureus (Fig 1B). However, SARS-CoV-2 infection was not associated with a statistically significant decline of epitope hits or EB scores for most other clinically relevant pathogens. Conclusion We assessed broad changes in the antibody repertoires of subjects prior to and after SARS-CoV-2 infection for clinically relevant pathogens at the epitope level by VirScan. Together these data suggest that SARS-CoV-2 infection is not associated with differential patterns of antibody repertoire kinetics for most non-coronavirus respiratory pathogens in immunocompetent adults. Further analyses in larger cohorts with longer follow-up are needed to confirm these findings. Disclosures Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Symbio: Advisor/Consultant Alpana waghmare, MD, Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|GlaxoKlineSmith: Advisor/Consultant|GlaxoKlineSmith: Grant/Research Support|Pfizer: Grant/Research Support|Vir: Advisor/Consultant

P-2362. Risk Factors for Persistent and Recurrent CMV DNAemia in a Real-World Cohort of SOT and HSCT Patients Receiving Maribavir

Abstract Background Refractory/resistant (R/R) CMV infection, defined by persistent symptoms or DNAemia after at least two weeks of antiviral therapy, is associated with high rates of rejection and mortality in transplant patients. Maribavir (MBV) is a newer agent with demonstrated efficacy in achieving DNAemia clearance without the bone marrow suppression associated with conventional first line therapy. However, there is less data on the risk factors for treatment failure with MBV. We sought to evaluate clinical outcomes of MBV in transplant patients in a real-world patient cohort.Table 1:Demographic Characteristics Methods A retrospective chart review was conducted of adult solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients who received MBV for R/R CMV infection at a high-volume transplant center from 2021-2023. The main treatment outcome was failure (defined as persistence of DNAemia requiring a switch in therapy).Table 2:Risk Factors for Maribavir Failure Results Nineteen patients received MBV for CMV DNAemia or tissue-invasive disease. Overall, 84% were SOT, 63% had high-risk CMV serostatus, and 90% had asymptomatic DNAemia. Twenty-six percent of patients experienced MBV failure. The median absolute lymphocyte count (ALC) was 852 µL at MBV switch in those with successful treatment compared with 262 µL in those with MBV failure, although this did not reach statistical significance. Peak viral load was also not significantly associated with MBV failure. Five patients later developed MBV resistance by commercial genotype sequencing. Conclusion Real world use of MBV demonstrated comparable rates of viral clearance with clinical trial data in SOT and HSCT patients. While not statistically significant, there was a trend towards MBV failure in patients with lower ALC. Future studies may be useful to determine if switching to MBV before onset of worsening lymphopenia related to first line therapy would impact the rate of treatment failure and MBV resistance. The lack of association between VL and virologic response also suggests that MBV may be safely used in patients regardless of viral load. Disclosures Joanna M. Schaenman, MD, PhD, FAST, Eurofins Viracor: Honoraria|F2G: Grant/Research Support|MedCure: Advisor/Consultant|Moderna: Clinical trial support to institution|OneLegacy: Advisor/Consultant

P-570. Infectious Disease Physician Office-Based HIV Program Results in Successful Adherence of Therapy in Patients Receiving Long-Acting Cabotegravir and Rilpivirine

Abstract Background The long-acting (LA) formulation of cabotegravir (CAB) and rilpivirine (RPV) demonstrated efficacy in Phase 3 studies and was approved in the US for HIV-1 in 2021. CAB+RPV LA offers treatment advantages over daily oral therapy with 1-2 month injections administered by a health care provider. However, onboarding of therapy and drug access for patients has proven challenging for physicians. We describe real-world implementation of a standardized Infectious Disease (ID) office-based CAB+RPV LA program with evaluation of adherence and virologic effectiveness. Methods The ID in-office CAB+RPV LA program was implemented in July 2023 in a national network of ID practices. The program involved creation of standardization for drug orders and approval, nurse training and appointment management. The first 100 patients treated in the program were followed. Data included demographics, prior therapy, baseline laboratory data, adherence to schedule and follow-up laboratory indices. Adherence was defined as injections received +/- 7 days from target date. Results Overall, 100 patients have entered the program in 20 practices nationally from July 2023 to March 2024. Median age is 49 years (IQR: 49-59), 81% male. Median weight and BMI are 89.8 kg (IQR: 80.8-101.6) and 29.2 kg/m2 (IQR: 27.1-31.9), respectively. Median duration of HIV disease is 7 years (IQR 4, 13) and patients received 1 (IQR: 1-2) oral regimen prior to CAB+RPV LA. A total of 55 patients initiated CAB+RPV LA in the ID physician office and 45 transferred care to their ID physician office. Median baseline viral load prior to any CAB+RPV LA was 30 (IQR: 21-65) and CD4 count was 761 (IQR: 535-1008). The majority (98%) are receiving injections every 2 months. Of 274 injections administered to date, 269 (98.2%) have been adherent to schedule. Fourteen patients eligible for 6 month follow-up labs had viral load undetectable (86%, n=12) or suppressed (14%, n=2). Six patients discontinued therapy, primarily due to financial or payor issues. Conclusion An ID physician office-based CAB+RPV LA program resulted in high levels of injection adherence. Patients eligible for follow-up achieved a 100% level of virologic control. These results suggest that CAB+RPB LA administered through a standardized ID office-based program is effective in managing HIV-1. Disclosures Nikhil K. Bhayani, MD, FIDSA, CorMedix: Advisor/Consultant|Cumberland Pharmaceuticals: Advisor/Consultant|Melinta: Advisor/Consultant|Paratek Pharmaceuticals: Advisor/Consultant Erika M. Young, DO, Cumberland Pharmaceuticals: Advisor/Consultant Brian S. Metzger, MD, MPH, Cumberland Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant Lucinda J. Van Anglen, PharmD, Cumberland Pharmaceuticals: Grant/Research Support|Ferring Pharmaceuticals: Grant/Research Support|Novartis Pharmaceuticals: Grant/Research Support|Takeda Pharmaceuticals: Grant/Research Support

P-1190. Viral Codetection in Infants with Respiratory Syncytial Virus (RSV) Infection Is Associated with Decreased Viral Loads, Reduced Mucosal Cytokine Concentrations and Longer Hospitalization

Abstract Background Studies have analyzed the contribution of host and viral factors to RSV disease pathogenesis and severity in children, but the role of RSV/viral co-detection is poorly understood. We investigated the relationship between viral co-detection, RSV viral loads, mucosal cytokine concentrations and disease severity in young children with RSV acute respiratory infection (ARI). Methods We enrolled a convenience sample of previously healthy children < 2 years of age with RSV ARI that were either hospitalized or managed as outpatients at a large pediatric hospital. Nasopharyngeal samples were obtained to assess RSV viral loads by rt-PCR, viral codetection using a multiplex PCR assay, and mucosal cytokine concentrations. We assessed the impact of viral co-detection on RSV viral loads, mucosal cytokine concentrations, and clinical outcomes stratified by age (0-6 and >6-24 months).Figure 1.Mucosal cytokine concentrations according to single RSV detection versus RSV/viral co-detection . The Y axis depicts individual concentrations of mucosal antiviral cytokines (IFN-β and CXCL-10) and of IL-6 expressed as log10 pg/ml, and the x axis the two study groups: single RSV infections and RSV/viral co-detections. Comparisons between groups were made with Mann-Whitney test and statistical significance was set at p< 0.05. Results From February 2013 to March 2020, 483 children with RSV ARI were enrolled (inpatients, n=383; outpatients, n=95). Of those, 108 (22.4%) had viral co-detection. Rhinovirus/Enterovirus (RV/EV) followed by endemic coronaviruses (CoV) were the most common co-detected viruses. Median age was 3.9 months for infants with RSV/viral co-detection vs 2.8 months for with single RSV ARI (p=0.02); with no significant differences in other demographic characteristics (Table 1). RSV loads were higher in single RSV vs RSV/viral co-detection (7.55 vs 7.16 log10 copies/ml, p=0.0009), particularly in infants 0-6 months. Mucosal concentrations of IL-6, CXCL-10, and IFN-β were significantly higher in children with single RSV vs RSV/viral co-detection (Figure 1). Analysis by age showed significant differences of IL-6 and CXCL-10 concentrations in infants 0-6 months, but not in older children. There were no significant differences with respect to need for hospitalization, clinical disease severity or PICU care in infants with single RSV vs RSV/viral codetections, but RSV/viral co-detection was associated with longer hospitalizations (3 vs 2.3 days respectively, p=0.022). Conclusion Concomitant detection of other respiratory viruses in children with RSV ARI was common and associated with reduced RSV viral loads, decreased mucosal proinflammatory and antiviral cytokines, and longer length of stay. Disclosures Diego R. Hijano, MD, MSc, FDA: Grant/Research Support|Merck: Grant/Research Support|National Institute of Health: Grant/Research Support Octavio Ramilo, MD, AstraZeneca: Honoraria|Bill & Melinda Gates Foundation: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|NIH/NIAID: Board Member|NIH/NIAID: Grant/Research Support|NIH/NICHD: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Honoraria Asuncion Mejias, MD, PhD, MsCS, Astra-Zeneca: Advisor/Consultant|Astra-Zeneca: Honoraria|Enanta: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi-Pasteur: Advisor/Consultant|Sanofi-Pasteur: Honoraria

P-555. Use of Long-Acting Cabotegravir/Rilpivirine in People Living with HIV with Renal Transplantation

Abstract Background Cabotegravir/Rilpivirine (CAB/RPV) represents a novel combination of long-acting injectable antiretroviral therapy (LAIART). Although the unique benefits of LAIART have been demonstrated in large clinical trials among people with HIV, including a favorable safety profile, few drug-drug interactions, and viral control without a daily oral pill requirement, evidence of LAIART use among PWH diagnosed with end-stage chronic kidney disease (CKD) and during kidney transplantation (KT) remains sparse. Detailed timeline of all 3 patients in the study. Methods A phase IV clinical trial CAPRI (NCT05601128) was designed to evaluate the pharmacokinetics and safety of long-acting CAB/RPV among PWH with CKD >= stage 4 or ongoing hemodialysis. Three enrolled participants were included, in this analysis because of their KT status, of them, one KT before the trial and two KT during the trial. The peri- and post-operative effects of CAB/RPV LA were evaluated focusing on viral load, CD4+ counts, and potential drug interactions. According to protocol, CAB/RPV PK samples were obtained and planned to be measured and analyzed. Results All three participants have been virally suppressed (< 50 copies/ml) by CAB/RPV LA with stable CD4+ counts while maintaining appropriate graft function during 12months of study period. The timeline for each participant was depicted in the Figure and details were summarized in terms of virologic and immunologic outcomes as well as renal function at different study periods. CAB/RPV LA was well tolerated, without major related adverse events noted. The renal function was significantly improved, dialysis free, in two participants receiving KT during the trial whereas it remained stable, dialysis free, in the participant with prior KT. The reported tacrolimus trough concentrations were maintained within the therapeutic range to protect the graft function. Conclusion The safety and efficacy of CAB/RPV LA have been observed in these participants, supporting its potential use among those with severe renal impairment and kidney transplantation. Additional advantages including lack of adherence barriers and low drug interaction potential are likely to increase viral suppression and improve overall quality of life in this special population. Disclosures Chiu-bin hsiao, MD, Viiv, Gilead: Grant/Research Support

P-490. Differentiation of Latent Versus Active HIV Infection at the Single Cell Level Using RT-ddPCR

Abstract Background With successful treatment of HIV, viral loads can drop to levels undetectable by regular qPCR diagnostic methods. However, the virus remains latent in cellular reservoirs . These reservoir cells are rare, and their quantification is a critical parameter to assess future HIV treatments. Digital PCR (dPCR) technology bypasses the limitation inherent to regular qPCR, and can quantify to some extent cells with latent HIV infection within a cell population. Methods Here we describe a protocol relying on dPCR that allows differentiation between active and latent infection at the single cell level. We used a digital droplet setting (ddPCR) that allows for reverse transcription (RT) within the droplet. The assay is multiplexed to detect both HIV proviral DNA as well as spliced mRNA indicative of HIV active replication. Briefly, single cell are isolated into droplet containing RT-ddPCR reaction, including the Bio-Rad Supermix One-Step RT ddPCR Advanced Kit and primers/probe sets targeting HIV genome gag in the FAMlow channel and the spliced 2kb class mRNA in the FAMhigh channel. After the RT-PCR reaction, the droplet fluorescence intensity was measured using a Bio-Rad Q200 droplet reader. Results We successfully evaluated HIV activation in cells lines with (8E5) or without HIV (CEM-T4) infection, as well as volunteer Peripheral Blood Mononuclear Cells (PBMC). We first determine the fluorescence bandwith for each target using DNA/RNA purified from cell lysate, identifying the HIV genomic DNA signal (FAMlow) between 2500 and 3500 MFI and the active replication signal (FAMhigh) between 4000 and 5000 MFI. We then repeated the RT-ddPCR reaction, this time using cells isolated in an excess of droplets (2000 cells for 15,000 droplet per reaction). Conclusion This Single Cell RT-ddPCR protocol allows for identification and quantification of HIV infected cells and assess their individual level of activation/latency. In the future, the multiplexing approach could be used to not only assess HIV activation, but also to identify cellular transcripts specific to latency or active replication. Disclosures All Authors: No reported disclosures

P-558. Long-acting Injectable Cabotegravir/Rilpivirine Plus Subcutaneous Lenacapavir Effective in People with HIV with Viremia and Cabotegravir or Rilpivirine Resistance-Associated Mutations

Abstract Background Long-acting antiretroviral regimens have the potential to achieve virologic suppression in people unable to maintain adherence to daily oral antiretroviral therapy (ART). Long-acting injectable cabotegravir/rilpivirine (LAI CAB/RPV) is currently the only complete long-acting regimen and is recommended by IAS-USA for select patients with viremia. However, resistance-associated mutations (RAMs) among treatment-experienced people with HIV are common, precluding use of LAI CAB/RPV. LAI CAB/RPV plus subcutaneous lenacapavir (LEN) may provide therapeutic options for people with poor long-term adherence and cabotegravir or rilpivirine RAMs.Table 1.NNRTI Mutations by Patient Methods Patients at UMMC’s Adult Special Care Clinic were selected for LAI CAB/RPV plus LEN by a multidisciplinary panel. Criteria for selection included recurrent viremia despite intensive case management strategies, presence of historical or current RAMs to CAB or RPV, and partially- or fully-active cabotegravir based on mutation scores. Patients began therapy with LEN and LAI CAB/RPV on the same day. The prescribed regimen consisted of CAB/RPV 600/900 mg intramuscular at months 0 and 1 followed by every 2 months and LEN 600 mg oral daily x 2 days and 927 mg subcutaneous every six months. No oral lead-in of CAB/RPV was administered, and oral LEN was administered via directly-observed therapy. Results Nine patients were treated with LAI CAB/RPV plus LEN at UMMC. Mean baseline viral load was 36 251 copies/mL. All patients had RPV RAMs. One patient had CAB RAMs (N155H, T977A) conferring low-level resistance to CAB. The follow-up period ranged from 24-36 weeks. All patients maintained viral loads < 200 copies/mL during follow-up. Patients with baseline CD4 < 200 cells/µL demonstrated 208% increase in absolute CD4 count. No treatment-emergent resistance has occurred to date. Conclusion LAI CAB/RPV plus LEN achieved virologic suppression for up to 36 weeks of follow-up in PWH with incomplete adherence to oral ART and mutations to CAB or RPV. Further follow-up and larger sample size will be needed to determine long-term durability of this combination. Additional combinations of long-acting ART are vitally needed to achieve virologic suppression for all. Disclosures All Authors: No reported disclosures

P-593. Does Dolutegravir increase hypercholesterolemia and/or hypertriglyceridemia?

Abstract Background Antiretroviral therapy improved prognosis of people living with HIV (PLWA). WHO recommends Dolutegravir as the preferred treatment option for HIV in all populations considering its high genetic barrier and rare adverse effects compared to other treatments. In Morocco, the transition to Dolutegravir has begun in 2020 with the regimen: tenofovir desproxil fumarate/lamivudine/dolutegravir TDF/3TC/DTG (TLD). Some studies shown increased cholesterol and triglycerides levels on TLD regimens. The purpose of this study is to compare the effect of TLD on cholesterol and triglyceride levels compared to other antiretroviral therapy (ART) regimens. Methods We conducted an observational comparative study at the Infectious diseases department Mohammed VI university hospital Marrakesh, MOROCCO. We included all PLWA admitted between 1st January 2021 and 31 December 2022 put on any ART and having a lipidic dosage. We excluded all patients with previous hypercholesterolemia and/or hypertriglyceridemia. We compared the occurrence of hypercholesterolemia and/or hypertriglyceridemia in PLHIV on TLD with those on other ART. For the statistical analysis a pearson chi-square test was used with the R software. Results We included 173 PLWA; the median age was 33 years. 66.5% were male. The viral load was available in 152 people and was < 1000 copies/mL in 98%. The CD4 count was available in 161 persons and was >200 cells/mm3 in 69.6%. There were 120 persons on TLD arm (69.36%) and 53 on other ART arm (30.64%). On the TLD arm 15 people (12.5%) and 16 (13%) have developped an hypercholesterolemia and/or hypertriglyceridemia respectively versus 10 (18.86%) and 12 (22.64%) have developped an hypercholesterolemia and/or hypertriglyceridemia respectively on the others ART arm, but the difference was statistically non-significant (X2= 0.74; p=0.38) for hypercholesterolemia and (X2= 1.47; p=0.22) for hypertriglyceridemia. Conclusion This study shows that there is no strong evidence of any association between the TLD regimen and the hypercholesterolemia and/or hypertriglyceridemia. The TLD regimen is more safe on the lipidic metabolism compared with other ART. Further large studies are needed to prove this benefit. Disclosures All Authors: No reported disclosures

P-477. What Can be Learned from Vermonters Living with HIV Viremia?

Abstract Background Lower rates of viral suppression have been identified in people living with HIV (PLHIV) residing in rural compared to metropolitan areas. This is a barrier to ending the HIV epidemic in the US, and thus represents an urgent focus topic. Vermont is a rural state with roughly 700 PLHIV. Vermonters living with HIV tend to be rigorously engaged into clinical care and have high rates of viral suppression. Yet, there are PLHIV in Vermont that have unsuppressed viral loads, and little is known about the characteristics of this cohort. Our study aims to epidemiologically describe Vermonters with an HIV viral load greater than 200 copies/mL. This characterization can aid in appropriate allocation of resources and improve our understanding of PLHIV with viremia residing in rural areas. Methods Our study used electronic health record data from Epic Systems Corporation (Epic) from 2019 and 2020. We included PLHIV from three infectious disease clinic sites within the University of Vermont Health Network (UVMHN; n = 456) that had at least one clinical visit in the past 18 months. The following data were extracted from patient charts: HIV detection and quantitation, clinic location, race, sexual orientation, and substance use. Results The results of our study are shown in Tables 1 and 2. There was no significant association between clinic location, race, sexual orientation, or substance use and having a viral load greater than 200 copies/mL. Conclusion Our results suggest that in Vermont, the presence of viremia in PLHIV cannot be easily predicted by clinic location race, sexual orientation, or substance use. The authors suggest that traditional clinical markers including low CD4 counts, HIV resistance mutations, pill burden, older age and concomitant clinical comorbidities (dementia, etc.) may be more reliable factors associated with active viremia. Although Vermont is demographically distinct from other rural areas, its residents share many barriers related to HIV care, including long travel distances to visits, limited HIV provider availability, and limited access to harm reduction services. These challenges necessitate our continued efforts to better understand and serve PLHIV living in rural areas to improve HIV equity and ultimately end the HIV epidemic. Disclosures All Authors: No reported disclosures

P-2192. Hepatitis C Virus Re-infection in the Direct-Acting Antiviral Era within the US Veterans Health Administration

Abstract Background Background and Aims: Hepatitis C virus (HCV) treatment with direct-acting antivirals (DAA) results in a sustained virologic response (SVR) in >90% of individuals (1). Limited prior data describes persons who achieve SVR and later develop recurrent viremia. We identify a cohort with HCV viremia after SVR, detail their risk factors for repeat viremia, and describe the time interval to repeat viremia Characteristics of Veterans with recurrent HCV viremia (n= 1129) Methods We identified individuals in the Veterans Health Administration in care during 2021-2022 who received DAAs between January 1, 2014 and December 31, 2022, achieved SVR, and developed repeat viremia. We performed a manual chart review of a randomly selected subset of patients (10%) who were adjudicated into four categories defined as: (1) definite reinfection (HCV genotype change after SVR), (2) presumed reinfection (injection drug use, HIV pre-exposure prophylaxis receipt, new HIV or hepatitis B diagnoses, or incarceration between SVR and repeat viremia), (3) false positive result based on clinician assessment, or (4) neither (possible late relapse). Adjudication as confirmed reinfection, probable reinfection, false positive, or neither based on chart review, N = 110 SVR = sustained virologic response; EOT = end of treatment; PrEP = pre-exposure prophylaxis VL = viral load. Results Among the 1,129 individuals in the cohort, median time to viremia after SVR was 23 months (IQR 9 – 42 months). Of the 110 individuals randomly selected for chart review, 25.5% (28/110) were definite reinfections, 25.5% (28/110) presumed reinfections, 11.8% (13/110) false positives, and 37.3% (41/110) did not meet any of the above criteria and were considered possible late relapses. Overall, 56/110 (50.9%) had a genotype change or known risk factor for reinfection, with IDU being the most common risk factor (27/110), followed by incarceration (10/110). Time to repeat viremia Conclusion Our study found the median time to repeat viremia is 1.9 years with 75% of individuals developing repeat viremia within 3.6 years. In detailed chart review of a random subset of individuals with repeat viremia, half had confirmed or probable reinfection, and a clinically significant minority were false positive. After EMR review, over one third had no identified risk factor for repeat viremia. (1) Nguyen V, et al. JAMA Netw Open. 2022;5(12). Disclosures All Authors: No reported disclosures

Analysis of HIV therapy in the liver using optimal control and pharmacokinetics

The main burden in treating human immunodeficiency virus (HIV) infection currently, is the side effects of the antiretroviral therapy (ART) used, because each treatment is toxic to the liver. This study uses optimal control theory applied to a mathematical model that describes the dynamics of HIV infection in the liver. The optimal controls are presented as therapy efficacy of reverse transcriptase inhibitors (RTIs), integrase inhibitors (INs) and protease inhibitors (PIs). An objective function is defined with an aim to investigate the optimal control strategy that minimises toxicity, viral load and cost of first-line and second-line HIV regimen. Results indicate that, in the first-line regimen with INs, a patient has to take medication for at least 98% of the treatment time and the regimen should be close to 100% efficacious regardless of the intervention cost. For second-line regimen, the period of drug administration of PIs largely depends on the weight constants. Inclusion of INs in the first-line regimen yields better HIV DNA suppression, as they are more efficacious than NRTIs. Of all drugs studied, nevirapine is highly efficacious but most toxic. The study recommends routine transaminase tests because results indicate liver enzyme elevation even with very low viral load. Numerical results with pharmacokinetic parameters further indicate an increase in HIV load at initiation of therapy, due to viral redistribution in plasma.

578. Metformin reduces the risk of Long COVID or Death over 6 months in an Emulated Target Trial of Primarily Omicron-infected Adults without Diabetes or Prediabetes: a New-User, Active-Comparator Analysis Using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database. This research was supported in part by the Intramural/Extramural research program of the National Center for Advancing Translational Science,

Abstract Background Metformin has decreased SARS-CoV-2 RNA in 4 cell lines. In a RCT of > 1,000 majority vaccinated outpatients, COVID-19 related ED visits/Hospitalization/Death occurred in 4.7% of the metformin vs 9.0% of the placebo group by Day 28; clinician-diagnosed Long Covid (LC) occurred in 6.2% of metformin vs 10.3% of placebo by Day 300; and 14% of metformin vs 23% of the placebo group had detectable nasal viral load on Day 10. In a trial of 20 adults, 60% of metformin vs 100% of placebo had detectable viral load by Day 4. Observational analyses report associations between prevalent metformin and less severe acute COVID. Given these data, we assessed whether metformin currently prevents LC. Cumulative Incidence Curve Cumulative incidence curves for the outcome of Long Covid/Death in the 180 Days after a metformin prescription (blue) or active comparator prescription (red). The increase in outcomes at Day 90 reflects the computable phenotype, which cannot be computed until 90 days after infection. Per data use requirements in the National Covid Cohort Collaborative (N3C), the starting number at risk is not shown due to small cell sizes or the ability to calculate small cell sizes. Methods We emulated a randomized trial of metformin vs. control in SARS-CoV-2-infected outpatients. Intervention: prescription for metformin within 6 days of infection. Control: prescription for fluvoxamine, fluticasone, ivermectin, or montelukast (drugs used off-label for Covid but clinical trials have shown no effect on acute COVID outcomes). Exclusions: age < 18; metformin or comparator prescribed within 365 days; indication for chronic metformin use; contraindication for metformin or control. Outcome: a composite of LC or Death (LC/D), LC defined by U09.9 or a symptom/condition based computable phenotype. We used entropy balancing to estimate the average treatment effect with a weighted log linear model. This is a forest plot showing metformin use versus active comparator use and the development of Long Covid/Death by Day 180. The black squares represent risk ratios (RR), and the lines represent 95% confidence intervals. The number of outcomes, denominators, and exact percentages are sometimes omitted so that cell sizes <10 are not able to be calculated, in accordance with the data use requirements in the National Covid Cohort Collaborative (N3C). The Pre-Omicron Era is larger than the Omicron era in both the Metformin and Comparator Cohorts, but the denominator for the Day 0-6 sample is not shown because of cell sizes <10. The subgroup of those with new Paxlovid use was too small to analyze, so we present only the subgroup who did not also receive a prescription for Paxlovid. Results After balancing, the standardized mean differences were < 0.01. Overall, most (5,787/9,660, 59.9%) were infected during Omicron. In the metformin and control groups, 16% and 17% were Black; 16% and 13% were Hispanic, respectively. In the metformin group, 10/248 (4.0%) developed LC/D vs. 21/248 (8.5%) in the control group, RR 0.47 (95% CI 0.25 to 0.89). For prescriptions on Days 0-1 relative to infection the RR was 0.39 (95% CI 0.12-1.24); for prescriptions on Days 0-14 the RR was 0.75 (95% CI 0.52-1.08). Cohort Balance Cohort balance of the standardized mean differences (SMD) before weighting (in pink), and after weighting (in teal), for the primary analysis. Conclusion Metformin prescribed within a week of SARS-CoV-2 infection was associated with a 53% reduction in LC/D. Anything between an 11% to 75% reduction in risk is highly compatible with our data. Important questions remain: are results consistent in randomized clinical trial data from adults with a normal body mass index and those previously infected with SARS-CoV-2.Table 1:Individuals who experienced death before the prescription could be started were excluded from the trial emulation to mimic both target trials (COVID-OUT and ACTIV-6), as they were both decentralized trials that entailed medication delivery to the home. Those who experienced hospitalization between -1 to 3 Days were also excluded to mimic the target trial: those who were hospitalized on Day -1 to 0 relative to infection could not have received and taken an outpatient prescription of metformin or comparator for their SARS-CoV-2; those hospitalized on Days 1 to 2 likely spent at least one day in the emergency department before hospitalization, so it is also unlikely that they received an outpatient prescription, obtained the prescription from a pharmacy, and took a dose before being hospitalized. Disclosures All Authors: No reported disclosures

P-565. A Prospective and Retrospective Observational Study of Multidrug-Resistant Patient Outcomes with and without Ibalizumab in a Real-World Setting: United States (PROMISE-US) Study Design and Baseline Characteristics

Abstract Background Multidrug resistance arises usually in people with HIV (PWH) with extensive prior exposure to antiretrovirals (ARVs). There is a need for further understanding of factors that impact the maintenance of virologic suppression in heavily treatment experienced (HTE) PWH in a real-world setting.Table 1:Baseline Characteristics PROMISE-US 1/2* Any regimen including the two drugs and may have additional ARVs in the OBR** cGSS was calculated as per Gonzalez-Serna et al. Journal of Antimicrobial Chemotherapy, 2017, P. 496 –503, https://doi.org/10.1093/jac/dkw455. Because commercial resistance testing is not available for ibalizumab, fostemsavir, or lenacapavir, all 3 agents are always considered fully active.*** Adverse events were only collected for subjects in Cohort 2.ARV, antiretroviral; cGSS, combined genotypic sensitivity score; FTR, fostemsavir; IBA, ibalizumab; INSTI, integrase strand transfer inhibitor; LEN, lenacapavir; MVC, maraviroc; NNRTI, non-nucleotide reverse transcriptase inhibitor; NRTI, nucleotide reverse transcriptase inhibitor; OBR, optimized background regimen; PI, protease inhibitor; RNA, ribonucleic acid. Methods PROMISE-US (CT.gov Identifier: NCT05388474) is a phase 4 multicenter, retrospective and prospective, observational, non-interventional registry study. The primary objective is to evaluate the long-term efficacy and durability of ibalizumab in combination with other ARVs by comparing the clinical outcomes of patients receiving ibalizumab treatment (Cohort 2; C2) vs. matched patients not receiving ibalizumab (Cohort 1; C1). This abstract describes the study design and baseline characteristics of the first 100 patients enrolled. Baseline is defined as the date of the latest treatment change event (the start date of ibalizumab in C2; the start date of standard of care in C1). Table 1: Baseline Characteristics PROMISE-US 2/2 *Any regimen including the two drugs and may have additional ARVs in the OBR **cGSS was calculated as per Gonzalez-Serna et al. Journal of Antimicrobial Chemotherapy, 2017, P. 496 –503, https://doi.org/10.1093/jac/dkw455. Because commercial resistance testing is not available for ibalizumab, fostemsavir, or lenacapavir, all 3 agents are always considered fully active. ***Adverse events were only collected for subjects in Cohort 2. ARV, antiretroviral; cGSS, combined genotypic sensitivity score; FTR, fostemsavir; IBA, ibalizumab; INSTI, integrase strand transfer inhibitor; LEN, lenacapavir; MVC, maraviroc; NNRTI, non-nucleotide reverse transcriptase inhibitor; NRTI, nucleotide reverse transcriptase inhibitor; OBR, optimized background regimen; PI, protease inhibitor; RNA, ribonucleic acid. Results By 8-Nov-2023, a total of 114 subjects were enrolled; 70 in 1, 44 in C2. Baseline characteristics, including race, ethnicity, sex, gender, and time since diagnosis, were well matched between both cohorts. The use of ibalizumab and the combination of ibalizumab plus lenacapavir was associated with HTE patients with higher HIV viral loads and declining CD4 T cells (p-values of 0.0629 and 0.0001, respectively, for C2 vs. C1). Combined genotypic sensitivity scores (cGSSs) were comparable between the two cohorts (Table 1). However, since commercial resistance testing is not available for all newer agents, which are considered fully active, this measure may overestimate regimen sensitivity in C2 subjects who were more likely to have these in their regimens. 80% of C2 subjects had been on ibalizumab for greater than 12 months. Ibalizumab was well-tolerated with no infusion reactions reported. Conclusion Ibalizumab was more frequently selected for use in advanced HTE patients with lower CD4 cell counts and higher viral loads than other regimens. Through better understanding of HTE patients’ treatments and long-term use of ibalizumab, this study will help further characterize the efficacy and safety profile of the agents used in combination for this population with high unmet need to help guide treatment selection. Disclosures Princy N. Kumar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Stocks/Bonds (Public Company)|Johnson & Johnson: Stocks/Bonds (Public Company)|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Stocks/Bonds (Public Company)|Moderna: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company)|Theratechnologies: Grant/Research Support|ViiV/GSK: Advisor/Consultant|ViiV/GSK: Grant/Research Support|ViiV/GSK: Stocks/Bonds (Public Company) Charlotte-Paige M. Rolle, MD, MPH, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|MSD: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Brinda Emu, MD, Genentech/Roche: Advisor/Consultant|Theratechologies: Advisor/Consultant Zachary Henry, MD, gilead: Advisor/Consultant|theratechnology: Advisor/Consultant Claudia Martorell, MD, Gilead Sciences: Grant/Research Support|Theratechnologies: Grant/Research Support|ViiV: Grant/Research Support Jihad Slim, MD, FACP, AbbVie: Grant/Research Support|AbbVie: Honoraria|AbbVie: Speaker Bureau|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Honoraria|Gilead Sciences, Inc.: Speaker Bureau|Merck: Grant/Research Support|Merck: Honoraria|Merck: Speaker Bureau|Theratechnologies: Advisor/Consultant|Theratechnologies: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Speaker Bureau R Brandon Cash, PharmD, Theratechnologies: Employee Kaitlin Anstett, PhD, Theratechnologies Inc.: Employee