CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

which most likely reflects both the ongoing decay and proliferation of the latent reservoir and, ARV pressure. RAMs were not always detected, and this lack of longitudinal stability enforces the need to consider an individual's treatment history and all past genotyping test results (and the detection sensitivities of reports) for treatment management.

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A Precision Randomized Trial of Hepatitis C Treatment Adherence Support Among 3000 PWID in India Shruti H Mehta 1 , Allison M. McFall 1 , Mihili P. Gunaratne 1 , Aylur K Srikrishnan 2 , Jiban J. Baishya 1 , Ashwini Kedar 2 , Amrose Pradeep 2 , Jayseelan Boobalan 2 , Bryan Lau 1 , Stephan Ehrhardt 1 , David Thomas 1 , Muniratnam S. Kumar 2 , Gregory M. Lucas 1 , Sunil Suhas Solomon 1 1 The Johns Hopkins University, Baltimore, MD, USA, 2 YR Gaitonde Center for AIDS Research and Education, Chennai, India Background: HCV elimination is unlikely without curing people who inject drugs (PWID). Many PWID will need additional support to achieve HCV cure, but resources are limited, particularly in low-and-middle-income countries. A precision approach could improve the efficiency of intervention delivery. The STOP-C trial evaluated whether HCV treatment outcomes could be optimized by tailoring adherence support to PWID need across community-based centers in 7 cities across India. Methods: We implemented a precision randomized trial where arm assignment probabilities varied by participants' estimated probability for HCV treatment failure. A prediction model generated a prognostic score that classified persons as low or high-risk for failure. Those at high-risk were randomized 3:2:1 to patient navigation + flexible directly observed therapy with ≥1 weekly dose observed (PN+DOT), PN contact ≥ every 2 weeks (PN only) or basic support. Those at low-risk were randomized 1:2:3 to PN+DOT, PN only or basic support. All had a history of drug injection and were treatment naïve; those with decompensated cirrhosis were excluded. All received sofosbuvir/velpatasvir once daily for 12 weeks. The primary outcome, sustained virologic response (SVR; HCV RNA < LLOQ 12 weeks after treatment completion) was compared by Poisson regression adjusted for site (intent to treat, missing=failure). Results: 3000 participants were recruited from Jan 2021-Dec 2022 (2048 low-risk, 952 high-risk). Compared with participants in the low-risk stratum, those in the high-risk stratum were more likely to be younger (median 27 vs. 31), experience homelessness (26% vs 6%) and report active drug injection (89% vs. 42%). 2798 (93%) completed SVR assessment. 49% and 63% achieved SVR in high and low-risk strata, respectively. In the high-risk stratum, SVR in PN+DOT was similar to PN only and basic support. In the low-risk stratum, SVR in PN+DOT was associated with a statistically significant 9% increase in SVR vs. basic support (adjusted relative risk [aRR] 1.09; p=0.04) but did not differ in PN only vs. basic support (Figure). Within strata, SVR significantly increased with better prognostic score (aRR per 10% decrease: 1.04 low-risk, 1.10 high-risk; p<0.01 for both). Conclusion: Greater adherence support or long-acting treatments may be required to improve cure rates among PWID at highest risk for failure. However, programs could use prognostic scores to target interventions more efficiently and proactively address barriers to treatment adherence.

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A Phase II Trial of 4 Weeks of Glecaprevir/Pibrentasvir for Early Hepatitis C Virus: ACTG A5380 Arthur Kim 1 , Minhee Kang 2 , Triin Umbleja 2 , Estevao P. Nunes 3 , Kristen Marks 4 , Chanelle Wimbish 5 , Daniel S. Fierer 6 , Annie Luetkemeyer 7 , Dimas Kleimann 8 , Sunil Suhas Solomon 9 , Leonard Sowah 10 , Beverly L. Alston-Smith 10 , David L. Wyles 11 , Susanna Naggie 12 , for the A5380 Study Team 1 Massachusetts General Hospital, Boston, MA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 Oswaldo Cruz Foundation - Fiocruz, Rio de Janeiro, Brazil, 4 Weill Cornell Medicine, New York, NY, USA, 5 Social & Scientific Systems, Silver Spring, MD, USA, 6 Icahn School of Medicine at Mt Sinai, New York, NY, USA, 7 University of California San Francisco, San Francisco, CA, USA, 8 Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil, 9 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 10 National Institute of Allergy and Infectious Diseases, Rockville, MD, USA, 11 Denver Health Medical Center, Denver, CO, USA, 12 Duke University, Durham, NC, USA Background: Shorter treatment courses have been effective in early hepatitis C (HCV) but are still longer than optimal. Shortening from 8-12 weeks to a single month simplifies treatment and may further facilitate the national plan of HCV elimination. Methods: A5380 was a prospective, phase II, single-arm multicenter trial evaluating the efficacy and safety of once daily oral glecaprevir/pibrentasvir (G/P) 300 mg/120 mg for 4 weeks in adults with early HCV. Early HCV was defined as new ALT elevation (≥5x ULN or >250 U/L if normal ALT in prior year, or ≥10x ULN or >500 U/L if no or abnormal ALT in prior year); or detectable HCV RNA with prior negative antibody (1st infection) or HCV RNA (re-infection) within 24 weeks prior to study entry. The primary endpoint was sustained virologic response, SVR12, defined as HCV RNA 80% using the 90% Wilson confidence interval (CI). Participants not achieving SVR12 were offered re-treatment. Results: Forty-five participants (98% male, 51% White, 27% Black, 31% Hispanic/Latino, median age 36 years (range 22-65) were enrolled from the U.S. and Brazil between Nov 2019 and Jan 2023; 27% reported a history of injection drug use, 84% were 1st HCV infections. 51% were people with HIV (PWH), with CD4 / HIV RNA reported in Table 1. Median time from diagnosis to entry was 31 days (IQR: 15-49). Median baseline HCV RNA was 5.3 log IU/mL (IQR: 3.3-6.0), 71% genotype 1; median ALT was 146 U/L (range: 22-3866). SVR12 was achieved in 38 of 45 (84%) participants (CI: 74%-91%) and 86% (CI: 76%-93%) excluding 1 participant lost to follow-up (LFU). SVR12 was 83% (CI: 66%-92%) in PWH and 86% (CI: 70%-94%) in those without HIV. There were no treatment-related serious adverse events. For the 6 participants with recurrent viremia at or before SVR12, median baseline HCV RNA was 6.3 log IU/mL (IQR: 5.8-7.1) and self-reported pill counts suggested good adherence. Re-treatment with salvage regimens resulted in SVR12 for 4 of 4 participants with treatment follow-up. Conclusion: Treatment of early HCV with 4 weeks of G/P resulted in clinically acceptable cure rates in people with or without HIV. Although SVR12 >80% could not be concluded from the CI, a planned analysis excluding LFU supports that the SVR12 proportion is >75%. As simplified treatment approaches are critical for HCV elimination, a 4-week G/P regimen should be tested in implementation programs aiming to cure early HCV.

Poster Abstracts

CROI 2024 203