CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

Methods: ACTG A5371 enrolled PWH ≥18 years of age on suppressive antiretroviral therapy (ART) with central adiposity, insulin resistance or pre diabetes and SLD (defined as ≥5% IHTG on MRI-PDFF). All participants received semaglutide for 24 weeks (titrated to 1mg sc weekly by week 4). IHTG content was measured by a central, blinded reader. Mean changes and 95% confidence intervals (CI) were estimated using linear regression. Spearman correlations assessed associations between outcome measures. Results: Participants (n=49) had median age 52 years, BMI 35 kg/m 2 , 39% Hispanic ethnicity and 33% Black/African American race; 43% were cis or trans women and 82% were on integrase strand transfer inhibitor- based ART. Semaglutide was well-tolerated, with only 2 possibly-related Grade 3 (1 nausea, 1 serotonin syndrome) and no Grade 4 adverse events. Mean baseline (standard deviation) IHTG was 12.7% (6.1%). Mean (95% CI) absolute and relative declines in IHTG were -4.2% (-5.4, -3.1) and -31.3% (-39.0, -23.6), respectively (both p<0.001); 29% of participants had complete resolution of MASLD (absolute IHTG <5%); and 58% had a ≥30% relative reduction in IHTG. Trends toward greater improvements in IHTG were seen in women, Hispanics, non-Hispanic whites and with increasing age. Significant improvements in weight, waist circumference, fasting glucose and triglyceride concentrations were also observed (Table). Improvements in IHTG correlated with weight loss on semaglutide (r=0.54, p<0.0001). Conclusion: Low-dose (1mg weekly) semaglutide is a safe and effective pharmacologic therapy for MASLD in PWH and shows evidence of broader cardiometabolic benefit. Further analyses will assess specific immunologic and inflammatory pathway changes with semaglutide therapy in PWH, including those that may be unique to this population. Trends in HIV and HCV Prevention Efforts and Incidence Among People Who Inject Drugs in Baltimore Eshan U Patel 1 , Becky Genberg 1 , Bryan Lau 1 , Jacqueline E. Rudolph 1 , Jacquie Astemborski 1 , Rachel E. Gicquelais 2 , Danielle German 1 , David D. Celentano 1 , David Vlahov 3 , Steffanie Strathdee 4 , Greg Kirk 1 , David Thomas 5 , Shruti H. Mehta 1 1 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 University of Wisconsin– Madison, Madison, WI, USA, 3 Yale University, New Haven, CT, USA, 4 University of California San Diego, La Jolla, CA, USA, 5 The Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: Advances in HIV and hepatitis C virus (HCV) prevention and treatment have led to plans to end the HIV epidemic and achieve HCV elimination by 2030. Data on long-term trends in the uptake of combination HIV/HCV prevention services and their impact on HIV/HCV incidence among people who inject drugs (PWID) are limited. Methods: The AIDS Linked to the IntraVenous Experience (ALIVE) study is a community-based cohort of PWID aged ≥18 years in Baltimore, Maryland with 5 enrollment periods: 1988-89, 1994-95, 1998, 2005-08, and 2015-18. We assessed trends in HIV and HCV seroincidence, prevalence of injection practices, self-reported use of prevention and treatment services, HIV viremia (>400 c/ mL) and HCV viremia (>500 IU/mL) using Poisson and logistic regression with generalized estimating equations. Data were censored at 12/31/2019 (prior to the COVID-19 pandemic). Results: Overall, 5,506 participants attended 68,107 semi-annual visits. At enrollment, median age was 37 years; 26% were female. Of 2,657 initially HIV seronegative participants, 282 seroconversions occurred over 18,452 person years (py). Of 593 initially HCV-seronegative participants, 115 seroconversions occurred over 3,576 py. HIV incidence declined from 4.1/100py in 1988-1992-a period without combination prevention services-to 0.5/100py in 1999-2001 (IRR=0.12 [95%CI=0.06-0.23]) and continued to decline to 0.1/100py in 2017 2019 (IRR=0.02 [0.00-0.13]) (Figure). Although HCV seroincidence similarly declined from 9.8/100py in 1988-1992 to 1.7/100py in 1999-2001 (IRR=0.18 [0.08-0.39]), it generally remained high thereafter (e.g., 4.0/100 py in 2017 2019). Early declines in HIV and HCV incidence were associated with declines in injection drug use (89% in 1988; 51% in 2001; 36% in 2019) and increases in prescribed methadone use (10% in 1988; 22% in 2001; 44% in 2019) and syringe services program use (36% in 1998; 44% in 2001; to 51% in 2019). Later declines

in HIV incidence were also associated with increases in ART use (55% in 2006; 96% in 2019) and declines in HIV viremia (63% in 2007; 36% in 2019). However, HCV seroincidence remained high during periods in which HCV treatment uptake increased (2% in 2014; 56% in 2019) and HCV viremia declined (84% in 2006; 36% in 2019). Conclusion: In a cohort of PWID, HIV and HCV seroincidence decreased over time corresponding with increased prevention efforts and behavioral changes; however, HCV seroincidence remained high. Intensified efforts are needed to achieve HCV elimination among PWID.

Oral Abstracts

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Preclinical Pharmacokinetic Assessment of a Hepatitis C Virus Long-Acting Injectable Formulation Usman Arshad 1 , Henry Pertinez 1 , Joanne Sharp 1 , Joanne Herriott 1 , Edyta Kijak 1 , Eduardo Gallardo-Toledo 1 , Andrew B. Dwyer 1 , Catherine Unsworth 1 , Alison C. Savage 1 , James J. Hobson 1 , Lee Tatham 1 , David Thomas 2 , Paul Curley 1 , Steve Rannard 1 , Andrew Owen 1 1 University of Liverpool, Liverpool, UK, 2 The Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: Eight weeks of daily, oral glecaprevir (G) and pibrentasvir (P) cures 98% of people with chronic Hepatitis C Virus (HCV) infection. However, major challenges, including medication adherence and loss of patients to follow-up, impede delivery of this combination. As such, 58 million people remain infected worldwide. A long-acting injectable (LAI) providing 8 weeks of pharmacokinetic exposure from a single administration would overcome many of these challenges by providing a one-shot cure. Moreover, G and P possess key physicochemical and pharmacokinetic properties shared by other LAI paradigms. Methods: G and P were co-formulated as a fixed dose combination LAI (250 mg/mL G, 250 mg/mL P). Dosing volumes of 0.075, 0.15 and 0.3 mL (representing active doses of 18.75, 37.5 and 75 mg) were administered to male Sprague Dawley rats (n = 4, 250-300 g) via intramuscular injections to the thighs. Plasma samples were collected from the tail vein over 13 weeks and livers were harvested at the end of the study. G/P concentrations were quantified in plasma and liver using validated LC-MS/MS. Results: Rat plasma concentration-time profiles for G and P demonstrated a dose-proportional increase in exposure (Fig. 1) with dose-linear increases in AUC for both G and P (AUC0-tlast, 106, 220 and 390 μg·h/ml [G] and 157, 346 and 513 μg·h/ml [P] at 18.75, 37.5 and 75 mg doses, respectively). A less-than-dose-proportional increase in C max was observed (1203, 3033 and 4334ng/ml [G] and 428, 799 and 907ng/ml [P] at 18.75, 37.5 and 75 mg doses, respectively). Doses of 37.5 and 75 mg maintained plasma exposures above the reported median human Ctrough for the oral product. For the 18.75 mg dose, G and P concentrations remained above the human Ctrough for 5 and 11 weeks, respectively. Liver:plasma concentration ratios were comparable to those previously reported after oral administration to rats for both drugs. No behavioural issues were encountered, animals gained weight throughout and no overt injection site issues were visible upon inspection. Conclusion: Preclinical data for a novel G/P LAI demonstrate sustained therapeutic concentrations in rats over a period of 13 weeks, exceeding the 8-week human target duration. Parenteral administration did not adversely affect hepatic penetration in comparison to the oral route. Further work is

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CROI 2024