Gregory Huhn’s research while affiliated with Infectious Diseases Society Of America and other places

Background Cabotegravir (CAB) long acting (LA) for pre-exposure prophylaxis (PrEP) was approved in the US in Dec 2021 to reduce the risk of sexually acquired HIV-1 infection. The Centers for Disease Control and Prevention (CDC) guidelines state that both HIV antigen (Ag)/antibody (Ab) and HIV RNA testing should be conducted prior to every injection. This analysis presents data on testing practices, effectiveness, adherence, and persistence in real world setting in the US.Table 1:Baseline Characteristics for those with at least 1 injection of CAB LA PrEP Methods Individuals initiating CAB LA PrEP were identified from electronic health records in the Trio Health cohort between Dec 2021- Jan2024. HIV testing within ±7 days of injection and HIV incidence were assessed among individuals with ≥ 1 injection of CAB LA. Incident HIV was defined as detectable HIV RNA +/- positive HIV Ag/Ab test. Adherence was assessed among those with ≥ 2 injections of CAB LA. As per label, the first 2 initiation injections are to be administered monthly followed by continuation injections every 2 months. On-time injections were defined as occurring within ±7 days of target date and discontinuations as 127 days without injections.Table 2:HIV Testing during Follow-up among Individuals with ≥1 injection of CAB LA for PrEP (N=526) Results Among the 526 individuals with ≥ 1 injections (median 5 [IQR: 3-8]; median follow-up 7 months [IQR: 3-14] [Table 1]), 34% had both HIV RNA and HIV Ag/Ab tests performed, and 63% had either test prior to all injections [Table 2]. HIV RNA tests were used less frequently than HIV Ag/Ab tests. Of 474 with ≥ 2 CAB LA injections, 76 (16%) had a delayed 2nd injection with a median of 22 days delay [IQR: 9-33] [Table 3]. Of 396 with continuation injections, 131 (33%) had delays with median of 1 delayed injection and median delay of 12 days [IQR: 3-29]. Ten (3%) individuals had 1 missed injection and none missed ≥ 2 injections. No incident HIV diagnoses were identified. The majority were persistent at 6 months (92%) and at 12 months (85%).Table 3:Delayed Injections among Individuals with ≥2 Injections of CAB LA for PrEP Conclusion These real-world data with long duration of follow-up and a large sample size further support that CAB LA for PrEP remains effective at preventing HIV acquisition. Injections were administered on time among the majority of initiators. HIV testing practices in this real-world setting did not align with the CDC testing guidelines among a significant proportion of users. No incident HIV diagnoses were identified, regardless of testing approach or injection timing. Disclosures Moti Ramgopal, MD, FACP, FIDSA, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Carolyn A. Brown, MSPH, PhD, ViiV Healthcare/GSK: Stocks/Bonds (Public Company) Andrew Frick, MS, Trio Health: Employee Janna Radtchenko, MBA, Trio Health: Employee Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds (Public Company)|ViiV Healthcare: Full Time Employee Leigh Ragone, MS, GlaxoSmithKline: Stocks/Bonds (Public Company)|ViiV Healthcare: Full time employee Jean A. van Wyk, MBChB, MFPM, ViiV Healthcare: Employee|ViiV Healthcare: Stocks/Bonds (Public Company) Karam Mounzer, MD, Epividian: Board Member|Epividian: Honoraria|GS: Advisor/Consultant|GS: Grant/Research Support|GS: Honoraria|Merck: Advisor/Consultant|THERA Technologies: Grant/Research Support|ViiV healthcare: Advisor/Consultant|ViiV healthcare: Grant/Research Support|ViiV healthcare: Honoraria Paul Benson, DO, ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Steven Santiago, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|Janssen: Honoraria Gregory Huhn, MD, MPHTM, Eli Lilly: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV Healthcare: Grant/Research Support Kenneth H. Mayer, MD, MPH, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|ViiV Healthcare: Grant/Research Support Rick A. Elion, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Honoraria|Proteus: Grant/Research Support|Trio Health: Employee|ViiV Healthcare: Advisor/Consultant Vani Vannappagari, MBBS, MPH, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Full time Employee|ViiV Healthcare: Stocks/Bonds (Public Company)

Background Outside of randomized controlled trials (RCTs), there are limited data regarding the acceptability of injectable long-acting cabotegravir + rilpivirine (LA-CAB+RPV) among persons living with HIV (PLWH). To evaluate acceptability, we describe participant-reported outcomes (PRO) of LA-CAB+RPV among a population underrepresented in RCTs. Setting Ruth M. Rothstein Core Center (CORE), large urban HIV clinic in Chicago, Illinois, USA Methods We interviewed PLWH prescribed LA-CAB+RPV who receive primary care at CORE. PRO endpoints included treatment satisfaction, tolerability of injections, reasons for switching to LA-CAB+RPV, and unexpected effects of LA-CAB+RPV. Mean and standard deviations (mean±SD) and proportions (%) are reported. Results Among respondents (N=150), 67% identified as Non-Hispanic Black, 24% Hispanic, 56% male; the average age was 43 years (SD:13.2), and 37% were ≥50 years old. Most respondents (93%) completed ≥3 injection appointments at the time of interview. The most common reasons for switching to LA-CAB+RPV were no longer wanting to take pills (89%) and trouble taking their pills daily (58%). Treatment satisfaction was high (6.7±0.5 out of 7). Two-thirds (61%) reported an unexpected aspect of their life improved. Pain from injections was common (98%), with a mean pain score of 4.3 out of 10. Among those reporting pain, half (47%) reported pain decreased after initial injection. Among participants reporting pain score >6 (n=36), most (78%) reported no improvement since initial injection. Conclusions We found high treatment satisfaction with LA-CAB+RPV in a diverse population. Participants reported moderate injection pain, which improved with time. Results suggest injectable LA-CAB+RPV will be met with acceptability across diverse participant populations.

Background Long-Acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first FDA-approved, complete, long-acting injectable antiretroviral therapy (ART) regimen. In clinical trials, LA-CAB/RPV has proven to be highly effective in maintaining virologic suppression in people living with HIV (PLWH) with virologic suppression, on a stable ART regimen, and no resistance to either agent. There is limited published real-world data regarding the efficacy, adherence, and discontinuation rates of LA-CAB/RPV, especially in populations underrepresented or excluded from clinical trials. The purpose of this study is to evaluate the real-world efficacy of LA-CAB/RPV in achieving and maintaining virologic suppression in PLWH. Methods We conducted a single-center retrospective chart review of HIV-1 positive adults receiving care at the Ruth M. Rothstein CORE Center, a safety-net system in Chicago. Patients were included if they received at least one dose of LA-CAB/RPV between January 1, 2022 and October 31, 2022. Results A total of 96 patients met inclusion criteria and were included in the study. Of these patients, the median age was 42.5, 79.2% were Black/African American, 54.2% were cisgender men, and 46.9% had a BMI of ≥ 30 kg/m2. Baseline HIV viral load was < 50 copies/mL in 97.9% of patients. Additional baseline characteristics are described in Table 1. Most (86.5%) patients initiated direct-to-inject LA-CAB/RPV with 98% solely initiating every 2-month dosing schedule. The median number of LA-CAB/RPV doses received was 4 (range, 1-15). Virologic suppression was defined as HIV viral load < 50 copies/mL. Of the 96 patients, 79 had HIV viral load data at week 4 with 99.7% of those being undetectable, 37 had data at week 12 with 100% of those being undetectable, and 62 had data at week 24 of which 96.8% were undetectable. Adherence rates to injections were high, with 96.3% given on-time and the discontinuation rate was 18.8% Conclusion LA-CAB/RPV was highly effective in achieving and maintaining virologic suppression among a large number of patients at an urban HIV clinic. This study is limited by short follow-up time during the program's initial scale-up phase. Additional long-term data are needed to determine long-term real-world efficacy, adherence, and discontinuation rates. Disclosures Gregory Huhn, MD, MPHTM, Clinical Care Options: Advisor/Consultant|Eli Lilly: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Medscape: Advisor/Consultant|Merck: Advisor/Consultant|Practice Point Communications: Advisor/Consultant|Ridgeback: Grant/Research Support|Trio Health: Advisor/Consultant|Viiv: Advisor/Consultant|Viiv: Grant/Research Support

Background We evaluated utilization of emtricitabine/tenofovir disoproxil fumarate or tenofovir alafenamide (F/TDF, F/TAF) among PN after the approval of F/TAF for PrEP in the US. Methods EMR and dispensing data from Trio Health HIV Research Network were used for this retrospective observational study. The study included HIV-negative PN ≥ 18 years with first dispense of daily oral PrEP (≥30-day supply) between 10/19-5/21 followed for ≥6 mo; individuals with hepatitis B or post-exposure prophylaxis were excluded. Prescription adherence, measured as proportion of days covered (PDC; mean and proportion with PDC ≥50, 70, and 80%) and time to regimen discontinuation (no drug >3 mo) or switch (TRD; Kaplan-Meier analysis) were compared between regimens. Characteristics associated with PDC and time to first regimen stop (switch/discontinuation) were evaluated using generalized linear regression and Cox proportional hazard models, respectively. Results Of 1330 PrEP starts, 86% (1144) were dispensed F/TAF vs 14% F/TDF (186). Baseline characteristics differed by regimen [Table 1]. While PDC was similar for both regimens, F/TAF had higher number of dispenses and mean days supplied vs F/TDF; mean days of follow-up were similar [Table 1]. F/TAF users had longer TRD (mean 20.2 vs 8.5 mo, Log-rank p< .001); median TRD was 3.9 mo for F/TDF and not reached for F/TAF [Figure 1]. A higher proportion of PN on F/TDF discontinued (46% vs 24% F/TAF) and switched (26% vs 2% F/TAF) their regimen (both p< .001). After accounting for gender, race, payer, age, high-risk behavior, F/TDF had a higher risk of discontinuation or switch (HR=4.9 CI 3.9-6.2); Black race was also associated with higher risk of discontinuation or switch [Table 2]. Results were similar when considering only discontinuation (censoring at time of switch or loss to follow up). Older age was identified as the primary driver of PDC controlling for other factors [Table 2]. Table 1.Characteristics of PN Individuals Dispensed Oral PrEP After October 2019 and PDC on First PrEP RegimenFigure 1.Time to PrEP Regimen Discontinuation or Switch (TRD, months)Table 2.Risk of First Oral PrEP Regimen Discontinuation or Switch and Characteristics Associated with Higher PDC Conclusion In this study PN adults dispensed F/TAF had greater number of dispenses, mean days supplied, and were less likely to discontinue or switch from F/TAF compared to F/TDF. Older age was the primary driver of increased PDC when considering other factors, including demographics, insurance and regimen. Disclosures Rick A. Elion, MD, Gilead Sciences: Advisor/Consultant|Trio Health: Employee|ViiV: Advisor/Consultant Joshua Gruber, PhD, Gilead Sciences: Employee Janna Radtchenko, MBA, Trio Health: Employee Megan Dunbar, PhD, Gilead Sciences: Employee Kenneth H. Mayer, MD, Gilead: Advisor/Consultant|Merck: Advisor/Consultant|ViiV: Advisor/Consultant Gregory Huhn, MD, MPHTM, Eli Lilly: Advisor/Consultant|Eli Lilly: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Jannsen: Advisor/Consultant|Jannsen: Grant/Research Support|Merck: Advisor/Consultant|Viiv: Advisor/Consultant|Viiv: Grant/Research Support Karam Mounzer, MD, Epividian: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Trio Health: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Grant/Research Support Anthony Mills, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Grant/Research Support.

Background Effectively interrupting the source of transmission is a critical step in ending the HIV epidemic. COMEBACK (NCT04519970) is a 48-week single-center study in Chicago implemented in September 2020, with its main objectives to reengage lost-to-care patients and rapidly reinitiate ART to promote VS and favorable PROs. Methods Adults off ART ≥2 weeks, without history of significant B/F/TAF resistance or renal impairment, were rapidly started on B/F/TAF upon reengagement after same day collection of baseline labs and PROs. A retention screening assessment was used to stratify participants into case management (CM) tiers: Minimal, Moderate, or Advanced. An acuity assessment tool was adapted to determine whether participants needed additional support based on retention and VS. Currently, 80 of the expected 100 subjects are enrolled and 55 have reached the 24-week timepoint. Baseline and 6-month endpoints were analyzed for these participants. Results At baseline (N=55), median age was 34 years (range, 24–62), with 92.6% Black and 72.2% cisgender male. Median CD4+ was 338 cells/mm3, with a median viral load 7,402copies/mL, (range, < 40–333,350, 16.3% VS). Median time off ART was 2.6 months (range, 0.5-243). For CM, participants were stratified into Minimal (71%) and Moderate (29%) tiers; none were identified as Advanced. Table 1 reflects tier shifts through 24 weeks. Shifts in CM intensity differs from the HIV adherence self-efficacy PRO completed within 24 weeks, indicating that at least 50% underestimated their need to integrate and maintain adherence to ART treatment. Forty of 55 participants (72.7%) were retained-in-care at 6 months, with VS in 61.8% (N=34/55) by intention-to-treat and 85% (N=34/40) by observed analysis. No resistance to B/F/TAF was detected through 6 months. Note: The table reflects patients retained on study at their week 24 endpoint. Conclusion VS was high for participants retained-in-care, but lapses in retention and shifts toward more intense CM were likely due to social determinants of health challenges, including incarceration, housing insecurity, and COVID-19-related disruptions in healthcare. Disclosures Gregory Huhn, MD, MPHTM, Eli Lilly: Advisor/Consultant|Eli Lilly: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Jannsen: Advisor/Consultant|Jannsen: Grant/Research Support|Merck: Advisor/Consultant|Viiv: Advisor/Consultant|Viiv: Grant/Research Support.

Young age has consistently correlated with lower adherence to PrEP in MSM. Digital medicine, a dynamic healthcare platform of wearable physiological sensors and mobile communication technology that can respond to medication non‐adherence rapidly, has the potential in promoting PrEP adherence. We evaluated the feasibility and acceptability of Proteus Discover (PD), a digital monitoring adherence system, to measure PrEP adherence and provide real‐time feedback among cisgender YMSM and transgender women.100 HIV‐negative young men and transgender women ages 16‐24 years were enrolled in a 24‐week randomized controlled cross‐over study to TDF/FTC coencapsulated with PD vs. TDF/FTC standard‐of‐care. Participants in the 12‐week PD arm received weekly SMS text messages to promote pill taking based on PD adherence data. Dried blood spots (DBS) were collected at 4‐week intervals for tenofovir diphosphate (TFV‐DP) in red blood cells as the referent and questionnaires were completed to assess acceptability, usability, and patterns of use. Linear mixed models analyzed the relationship between 30‐day adherence measured by DBS and PD. PrEP adherence was high overall. Adherence, as measured by DBS, was correlated with adherence as measured by PD (p‐value = 0.03). Most participants reported that PD helped them take their PrEP daily and that the system was easy to use. However, a majority (53.5%‐60.5%) disagreed with the statement that wearing the patch was not an issue. There was an incremental increase in TFV‐DP in DBS with adherence by PD. More research is warranted to explore optimizing PrEP adherence for youth through real‐time monitoring.

Background The humoral response to SARS-CoV-2 can provide immunity and prevent reinfection. However, less is known about how the diversity, magnitude, and length of the antibody response after a primary infection is associated with symptoms, post-infection immunity, and post-vaccinated immunity. Methods Cook County Health employees provided blood samples and completed an online survey 8–10 weeks after a PCR-confirmed positive SARS-CoV-2 test (pre-vaccinated, N = 41) and again, 1–4 weeks after completion of a 2-dose series mRNA BNT162b2 COVID-19 vaccine (post-vaccinated, N = 27). Associations were evaluated between SARS-CoV-2 antibody titers, participant demographics, and clinical characteristics. Antibody titers and angiotensin-converting enzyme 2 (ACE2) neutralization were compared before and after the mRNA BNT162b2 COVID-19 vaccine. Results Antibody titers to the spike protein (ST4), receptor binding domain (RBD), and RBD mutant D614G were significantly associated with anosmia and ageusia, cough, and fever. Spike protein antibody titers and ACE2 neutralization were significantly higher in participants that presented with these symptoms. Antibody titers to the spike protein N-terminal domain (NTD), RBD, and ST4, and ACE2 IC50 were significantly higher in all post-vaccinated participant samples compared to pre-vaccinated participant sample, and not dependent on previously reported symptoms. Conclusions Spike protein antibody titers and ACE2 neutralization are associated with the presentation of anosmia and ageusia, cough, and fever after SARS-CoV-2 infection. Symptom response to previous SARS-CoV-2 infection did not influence the antibody response from subsequent vaccination. These results suggest a relationship between infection severity and the magnitude of the immune response and provide meaningful insights into COVID-19 immunity according to discrete symptom presentation.

Background Neutralizing monoclonal antibodies (mAbs) to SARS-CoV-2 are clinically efficacious when administered early, decreasing hospitalization and mortality in patients with mild or moderate COVID-19. We investigated the effects of receiving mAbs (bamlanivimab alone and bamlanivimab and etesevimab together) after SARS-CoV-2 infection on the endogenous immune response. Methods Longitudinal serum samples were collected from patients with mild or moderate COVID-19 in the BLAZE-1 trial who received placebo (n=153), bamlanivimab alone [700 mg (n=100), 2800 mg (n=106), or 7000 mg (n=98)], or bamlanivimab (2800 mg) and etesevimab (2800 mg) together (n=111). A multiplex Luminex serology assay measured antibody titers against SARS-CoV-2 antigens, including SARS-CoV-2 protein variants that evade bamlanivimab or etesevimab binding, and SARS-CoV-2 pseudovirus neutralization assays were performed. Results The antibody response in patients who received placebo or mAbs had a broad specificity. Titer change from baseline against a receptor-binding domain mutant (Spike-RBD E484Q), as well as N-terminal domain (Spike-NTD) and nucleocapsid protein (NCP) epitopes were 1.4 to 4.1 fold lower at day 15-85 in mAb recipients compared with placebo. Neutralizing activity of day 29 sera from bamlanivimab monotherapy cohorts against both spike E484Q and beta variant (B.1.351) were slightly reduced compared with placebo (by a factor of 3.1, p=0.001, and 2.9, p=0.002, respectively). Early viral load correlated with the subsequent antibody titers of the native, unmodified humoral response (p<0.0001 at Day 15, 29, 60 and 85 for full-length spike). Conclusions Patients with mild or moderate COVID-19 treated with mAbs develop a wide breadth of antigenic responses to SARS-CoV-2. Small reductions in titers and neutralizing activity, potentially due to a decrease in viral load following mAb treatment, suggest minimal impact of mAb treatment on the endogenous immune response.

Background Although studies show most COVID-19 survivors have post-infection immunity against SARS-CoV-2 that could prevent re-infection, there is still a need to identify the breadth of antibody (Ab) responses associated with clinical phenotypes. We characterized Ab profiles at the estimated peak of Ab diversity among adults with recovered SARS-CoV-2 infections and determined their relationships with clinical factors. Methods From April-June 2020, 41 health system employees with PCR-confirmed symptomatic COVID-19 infection enrolled 8-10 weeks after symptom onset. Symptom questionnaires including baseline demographics, COVID-19 symptoms, disease severity, and disease duration were collected and plasma samples were assayed using a custom Luminex Multiplex platform (Figure 1) to measure the antibody response against 20 COVID-19 related antigens (Figure 2). Differences in Ab profile titers among different groups were tested using nonparametric t test and Benjamini-Hochberg adjustment for multiplicity. Associations were considered significant at FDR< 0.05. Figure 1: Description of the Luminex Serology Assay Figure 2: List of the COVID-19 Related Antigens and Controls Measured Results Mean age was 48 years (range 27-68), with 51% female, 37% White, 32% Black, 29% Asian, and 17% LatinX. Ab profiles (Figure 3) showed 100% cross-reactivity with related alpha and beta coronavirus, and 95% with SARS-CoV-1. 78% had Abs against SARS-CoV-2 nucleocapsid protein (NCP). However, 29% of patients had no immune response against the four spike protein epitopes. These participants also reported fewer symptoms, including no cases of anosmia/ageusia, suggesting mild illness. Anosmia/ageusia, fever, and cough associated significantly with higher Ab titers (Figure 4). Conclusion Broad immune responses to various SARS-CoV-2 and related antigens were found among a heterogeneous patient population. However, less than 3 months after symptom onset, protective Ab responses to SARS-CoV-2 spike proteins were not detected in nearly one-third of recovered patients, primarily with mild infection. Intact sense of smell and taste demonstrated the greatest association with loss of seroprotective SARS-CoV-2 Ab responses, which may be clinically useful to predict post-infection immunity. Next steps include comparing the magnitude of Ab responses following full series completion with mRNA vaccination among this cohort. Disclosures Robert Bencshop, PhD, Eli Lilly (Employee) Josh Poorbaugh, PhD, Eli Lilly (Employee) Ajay Nirula, MD/PhD, Eli Lilly (Employee, Shareholder) Lin Zhang, PhD, Eli Lilly and Company (Employee, Shareholder) Stephanie Beasley, BA, Eli Lilly (Employee)

Numerous studies have detected a greater likelihood of excess weight gain with specific antiretrovirals (ARV’s), particularly tenofovir alafenamide and integrase inhibitors, as compared to other agents and classes. The long-term implications and potential reversibility for individuals who have experienced substantial ARV-associated weight accumulation remain poorly understood. Furthermore, the underlying mechanism remains controversial: is the explanation mitochondrial toxicity and weight suppression from the older agents or direct effects of the newer drugs on appetite, adipocytes, or other unintended targets? This review discusses proposed mechanisms and evidence to date and argues that the question about mechanism is highly clinically relevant because it carries significant implications for ARV management. The existing literature suggests that older ARV’s, such as tenofovir disoproxil fumarate and efavirenz, suppress weight gain, but also that integrase inhibitors may stimulate excess weight gain through several pausible biologic pathways. Confirming the mechanisms of ARV-associated excess weight gain should be high priority for future research.