CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: Using electronic health record data from health systems in Minnesota and Nevada, we identified oral antiviral-eligible SARS-CoV-2 patients between April 2022 and June 2023 as those ≥50 years old, unvaccinated, or with ≥1 high-risk medical condition. Modified Poisson regression was employed to estimate adjusted risk ratios (RRs) for the association between nirmatrelvir ritonavir (NMV/r) or molnupiravir (MPV) treatment and hospitalization within ≤14 days after the positive test, stratified by immunocompromised status. Using adjusted RRs and treatment prevalence, we also calculated the preventable fraction of hospitalizations that could have been averted had all eligible patients been treated. Results: Among 3,525 SARS-CoV-2 patients with risk factors for severe COVID-19, 2,223 (63.1%) were ≥50 years old (35.4% ≥65), 829 (23.5%) were unvaccinated, and 2,932 (83.2%) had ≥1 high-risk medical condition. Overall, 1,033 (29.3%) were prescribed an oral antiviral agent (911 NMV/r; 122 MPV) and 300 (8.5%) were hospitalized. Only 1.9% of treated patients vs. 11.2% of untreated patients were hospitalized (p<0.001). In adjusted analyses, treatment with any oral antiviral agent (RR=0.18), with NMV/r (RR=0.21), and with MPV (RR=0.05) were each significantly associated with a lower risk of hospitalization (Figure). The protective association for any antiviral was stronger in immunocompetent (RR=0.11) vs. immunocompromised (RR=0.37) patients (interaction, p<0.001). If all patients had been treated, 76.8% (95% CI: 66.6 85.9) of all hospitalizations could have been averted, including 85.7% (95% CI: 74.5-94.9) of those in immunocompetent and 54.9% (95% CI: 32.4-77.6) of those in immunocompromised patients. Conclusion: Three-quarters of COVID-19 hospitalizations in high-risk patients could have been prevented had all patients received oral antiviral treatment prior to disease progression. This noteworthy finding is attributed to the strong observed protective effect of treatment coupled with large treatment gaps. Moreover, the diminished protection among immunocompromised patients underscores the importance of close symptom monitoring and consideration of additional therapeutic options such as remdesivir and COVID-19 convalescent plasma. Pooled Analysis of Randomized Trials Comparing Drug Efficacy for Early COVID-19 During Omicron Waves Valentina Mazzotta 1 , Fulvia Mazzaferri 2 , Simone Lanini 1 , Massimo Mirandola 2 , Alessandro Cozzi-Lepri 3 , Alessandra Vergori 1 , Alessia Savoldi 2 , Francesca Bai 4 , Gaia Maccarrone 2 , L. Sarmati 5 , Carlo Tascini 6 , Enrico Girardi 1 , Annamaria Cattelan 7 , Andrea Antinori 1 , Evelina Tacconelli 2 1 IRCCS Lazzaro Spallanzani, Rome, Italy, 2 University of Verona, Verona, Italy, 3 University College London, London, United Kingdom, 4 Azienda Ospedaliera San Paolo, Milan, Italy, 5 University of Rome Tor Vergata, Rome, Italy, 6 Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy, 7 Azienda Ospedaliera di Padova, Padua, Italy Background:Antivirals and monoclonal antibodies are largely used for early treatment of COVID-19 in high-risk people, based on data from randomized trials (RCTs) among unvaccinated people before the omicron era. No evidence from RCTs is available on the comparison of clinical efficacy of currently available treatments. We present a pooled analysis of two RCTs conducted in Italy during omicron waves. Methods: MANTICO (EudraCT 2021-002612-31) and MONET (EudraCT 2021 004188-28) are two multicentric, open-label, phase 4 RCTs supported by the Italian Drug Agency. Non-hospitalized patients (pts) with early COVID-19 (≤5 days after symptoms onset) and >=1 risk factor were randomized 1:1:1 to receive 500 mg of intravenous sotrovimab (SOT) or 600 mg of intramuscular tixagevimab/cilgavimab (T/C) or oral 5-days course of nirmatrelvir/ritonavir (N/r) 300/100 mg BID. Primary outcome was COVID-19-related hospitalization or death within 29 days after randomization. Fisher's exact test for pooled data and incidence of failure was reported as overall and by arm with respective 95% CI. Exact logistic regression models were implemented to estimate differences between arms and to adjust for residual confounding (age, sex, and variables with imbalance >=5%). Secondary outcome analysis on the variation of

659

Nirmatrelvir/Ritonavir Reduces COVID-19 Symptom Duration Across Subgroups of Patients at High Risk Heidi Leister-Tebbe , Weihang Bao , Wayne Wisemandle, Romina Quercia , Jennifer Hammond, James Rusnak Pfizer, Inc, Groton, CT, USA Background: Nirmatrelvir with ritonavir (nirmatrelvir/r) is an oral antiviral treatment for COVID-19. We report times to sustained alleviation and resolution of COVID-19 symptoms, overall and across subgroups of non-hospitalized adults with COVID-19 at increased risk of severe disease treated with nirmatrelvir/r compared to placebo (PBO). Methods: EPIC-High Risk (HR) was a Ph 2/3 double-blind, randomized, PBO-controlled study to evaluate nirmatrelvir/r in symptomatic, unvaccinated, nonhospitalized patients (pts) with ≥1 risk factor for progression to severe COVID-19. Eligible adults with confirmed SARS-CoV-2 and ≤ 5 days (d) of symptoms were randomized 1:1 to nirmatrelvir/r 300 mg/100 mg or PBO every 12 hrs for 5 d. Pts logged presence and severity of prespecified COVID-19 symptoms daily Day 1 through 28. Times to sustained alleviation and resolution of all targeted symptoms within pt subgroups were assessed and compared between treatment groups using a COX proportional hazard model. Results: Among 2113 randomized pts, 1996 (nirmatrelvir/r, n=977; PBO, n=989) were included in the analysis population (≤ 5 d of symptom onset, did not/not expected to receive an mAb). Nirmatrelvir/r significantly reduced the times to sustained alleviation (median 13 vs 15 d, Hazard Ratio [HR]=1.27, p<0.0001) and resolution (16 vs 19 d, HR=1.20, p=0.0022) of all targeted symptoms through Day 28. Reduction in median time to sustained alleviation was observed in nirmatrelvir/r treated pts in all subgroups by baseline symptom severity, serostatus, viral load (VL), time since symptom onset, sex and age; with largest reductions among pts with moderate/severe symptoms at baseline (13 vs 17 d; p=0.0001), seronegative pts (13 vs 17 d; p=0.0001), pts with baseline VL ≥7 log 10 copies/mL (14 vs 19 d; p<0.0001), and pts >60 years of age (13 vs 18 d, p=0.0024) (Figure 1). The reduction in median time to sustained symptom resolution was more apparent in the same subgroups: pts with moderate/severe symptoms at baseline (20 vs 23 d; p=0.0101), seronegative pts (19 vs 23 d; p=0.0086), pts with baseline VL ≥7 log 10 copies/mL (19 vs 25 d; p=0.0272), and pts >60 years of age (18 vs 22 d, p=0.0386). Conclusion: Nirmatrelvir/r treatment reduced median times to sustained alleviation and resolution of all targeted COVID-19 symptoms vs PBO significantly overall, and consistently across pt subgroups (by baseline symptom severity, serostatus, VL, time since symptom onset, sex and age) in pts at high risk for progressing to severe disease.

Poster Abstracts

661

660

Large Fraction of COVID-19 Hospitalizations Preventable With Oral SARS-CoV-2 Antiviral Treatment Matthew E Levy , Evanette Burrows, Vanessa Chilunda, Dana Wyman, Andrew Dei Rossi, Hang Dai, Magnus Isaksson, Lisa McEwen, Nicole L. Washington, Tracy Basler, Kevin Tsan, Jason Nguyen, Jimmy Ramirez, Efren Sandoval, Shishi Luo Helix, San Mateo, CA, USA Background: Oral SARS-CoV-2 antiviral agents are an important treatment option for preventing severe COVID-19. We aimed to quantify the reduction in hospitalizations achievable through complete compliance with oral antiviral treatment guidelines in high-risk adults.

CROI 2024 189