CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

669

Viral and Symptom Rebound After COVID-19 Monoclonal Antibody Therapy in the ACTIV-2 Trial Kara W Chew 1 , Brooke McGinley 2 , Carlee Moser 3 , Jonathan Z. Li 4 , Teresa H. Evering 5 , Justin Ritz 3 , David Margolis 6 , David Wohl 7 , Michael D. Hughes 3 , Eric Daar 8 , Judith S. Currier 1 , Joseph J. Eron 7 , Davey M. Smith 9 , for the ACTIV-2/A5401 Study Team 1 University of California Los Angeles, Los Angeles, CA, USA, 2 Boston University, Boston, MA, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 Harvard Medical School, Boston, MA, USA, 5 Weill Cornell Medicine, New York, NY, USA, 6 Brii Biosciences, Inc, Durham, NC, USA, 7 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 8 Harbor–UCLA Medical Center, Torrance, CA, USA, 9 University of California San Diego, La Jolla, CA, USA Background: Risk of viral and symptom rebound after monoclonal antibody (mAb) therapy for COVID-19 is unknown. Methods: Viral and symptom rebound in a randomized placebo-controlled trial of combination mAbs Amubarvimab/Romlusevimab (A/R), which had been shown to reduce hospitalization/death by 79%, were explored. Symptom relapse was defined as first occurrence of any moderate/severe symptom (13 symptoms recorded in a daily 29-day diary) persisting for ≥2 consecutive days, after meeting a 2-days sustained symptom improvement or resolution endpoint. End of relapse was defined as the last day with any moderate/severe symptom after improvement or any mild/moderate/severe symptom after resolution. Viral rebound was defined as anterior nasal SARS-CoV-2 RNA ≥3 log 10 copies/mL at day 7, 14, or 28 that was ≥0.5 log 10 copies/mL higher than day 3, or at day 14 or 28 that was ≥0.5 log 10 copies/mL higher than day 7. Wilcoxon rank sum tests compared symptom outcomes by arm, by ranking participants in four ordered categories: 1) improved and never relapsed ordered by symptom duration; 2) improved but relapsed ordered by total time with symptoms; 3) never improved ordered by last available total symptom score (TSS, summing scores for all 13 symptoms on that day); 4) deaths. Joint modeling of time to improvement and to relapse assessed the risk of relapse among those with improvement or resolution, adjusting for day 0 TSS. Proportion of participants with viral rebound was compared between arms using Fisher's Exact test. Results: 784 participants were included. Median age was 49 years; 52% female (>99% cisgender); 72% White and 49% Latino/Hispanic. 75% A/R and 73% placebo participants achieved symptom improvement; 5% in each arm had symptom relapse (Table). 1 placebo participant with relapse was hospitalized. Fewer participants met symptom resolution (64% A/R, 60% placebo) and relapse after resolution (3% and 2%, respectively, none subsequently hospitalized) (Table). Time to symptom relapse did not differ between arms among those who achieved improvement or resolution (Table). Viral rebound occurred in 4% in each arm (p>0.99). 3 participants with viral rebound were hospitalized, all in the placebo arm. <1% of each arm experienced both symptom and viral rebound. Conclusion: This randomized trial found no significant differences in symptom experiences or viral rebound between mAb- vs placebo-treated participants. With or without treatment, rebound rates were low following sustained symptom improvement or resolution.

sub-variants of SARS-CoV-2 was rarely investigated and long-term incidence data are lacking Methods: Observational study of pts with HD who received 300 mg of T/C given intramuscularly as PrEP over MAR22-AUG23. Demographic and clinical characteristics were collected; BTIs were defined as a confirmed diagnosis by RT-PCR and clinical picture. The incidence of BTI (95%CI) was calculated using the Kaplan-Meier method. Factors associated with the risk of BTI were evaluated using a Cox regression model with fixed covariates after controlling for age, sex, type of HD and other comorbidities. The incidence of BTI was also calculated according to the circulating variant (VoC) as number of BTI per 100 PYFU. A Poisson regression adjusted for the same potential confounders was used to estimate relative rates of BTI by current VoC Results: N=501pts:68% initiated T/C PrEP when BA.5 was the most prevalent, followed by XBB/EG, BA.2 and BA.1 (21%, 7% and 3%, respectively); 46% female, median age 64 years (IQR 55, 73) and a median follow-up post treatment of 162 (92-297) days. HD were non-Hodgkin Lymphoma (NHL) 66%, Multiple Myeloma (MM) 12%, Chronic Lymphocytic Leukemia (CLL) 14%, Hodgkin Lymphoma (HL) 8%; 3% received CAR-T and 9% bone marrow transplantation. 87% received 3-4 vaccine doses 60% had other comorbidities. Overall, the 1-year incidence estimate of BTIs was 21% (16.5-26.8%), with a cumulative risk which was higher the longer the time since PrEP. A greater risk of incident BTIs was observed when BA.5 and XBB/EG sub-lineages circulated as prevalent in Lazio region [aRR 5.08 (2.18, 11.83); p<.001 and 3.77 (1.48, 9.60); p=0.005, compared to BA.1, respectively]. The 6-month incidence of BTIs was higher for MM [25%; 2-47%] than that seen for other HDs. Severe COVID-19 occurred in 6 pts, 4 deaths due to COVID-19 were reported. Conclusion: One-year incidence of BTIs after T/C PrEP was <25%, although increasing over time, possibly due to vanished neutralizing activity. The risk appears to be higher when more recent omicron sub-lineages were circulating Background: COVID-19 vaccination prevents severe manifestations, hospitalization, and mortality in healthy patients. Immunocompromised populations have a higher risk of complications, but poorer responses to vaccination. Long-acting monoclonal antibodies Tixagevimab/Cilgavimab effectively prevented COVID-19 and improved clinical outcomes when administered early after infection. They were approved for emergency use in ≥40 kg and ≥12 years old immunocompromised patients. Few studied its use in young children. This trial assessed the immunogenicity and safety of an alternative dose in immunocompromised 20-<40 kg children and adolescents. Methods: 6–18-year-old immunocompromised patients were enrolled in this single-center, prospective, open-labelled, randomized clinical trial. Participants were divided into two groups by body weight: 150-mg-Tixagevimab/150 mg-Cilgavimab (20-<40 kg) and 300-mg-Tixagevimab/300-mg-Cilgavimab (≥40 kg). Anti-SARS-CoV-2 receptor binding domain IgG (anti-RBD IgG) and pseudovirus neutralizing antibody (NAb) titers were measured as primary outcomes 4, 12, and 24 weeks after administration. Immunogenicity data at 4 weeks was compared with reference data from 5-11-year-old healthy children 2 weeks after a third dose of 10-µg-BNT162b2. Adverse events were closely monitored by telephone calls up to 7 days after administration. Results: Of 59 enrolled participants, 49.2% were female, with a median (IQR) age of 12 (9, 15) years. Fourteen children (24%) had malignancies. Four weeks after administration, similarly high levels of anti-RBD IgG geometric mean concentrations were observed for both arms (6,871 vs 7,486 BAU/mL in 20-40 kg, respectively; P = 0.446), and significantly higher levels than the reference (3,842 BAU/mL two weeks after three doses of BNT162b2; P < 0.001). NAb geometric mean titers (GMTs) for the ancestral Wuhan strain in both arms were similarly high (16,363 vs 17,675 BAU/mL in 20-40 kg, respectively; P = 0.468) and significantly higher than the reference (836 BAU/mL; P < 0.001). NAb GMTs for Omicron BA.4/5 in both arms were on par with the reference. Most adverse events were mild and well-tolerated. suggesting a lack of in vitro neutralization due to viral escape. The figure, table, or graphic for this abstract has been removed. Immunogenicity of Tixagevimab/Cilgavimab for COVID-19 in Immunocompromised Children and Adolescents Jassada Buaboonnam 1 , Supattra Rungmaitree 1 , Nuntawan Piyaphanee 1 , Sirirat Charuvanij 1 , Onsiri Pitisuttithum 2 , Katherine Copeland 1 , Chatkamol Pheerapanyawaranun 1 , Suvimol Niyomnaitham 1 , Kulkanya Chokephaibulkit 1 1 Mahidol University, Bangkok, Thailand, 2 AstraZeneca, Bangkok, Thailand

Poster Abstracts

671

670

Risk of SARS-CoV-2 Infection in Patients With Hematologic Diseases Receiving Tixagevimab/Cilgavimab Alessandra Vergori 1 , Alessandro Cozzi-Lepri 2 , Marta Chiuchiarelli 3 , Valentina Mazzotta 1 , Elisabetta Metafuni 3 , Giulia Matusali 1 , Valentina Siciliano 3 , Jessica Paulicelli 1 , Eleonora Alma 3 , Agostina Siniscalchi 4 , Elisabetta Abruzzese 5 , Simona Sica 3 , Massimo Fantoni 3 , Andrea Antinori 1 , Antonella Cingolani 3 1 Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy, 2 University College London, London, United Kingdom, 3 Catholic University of the Sacred Heart, Rome, Italy, 4 San Filippo Neri Hospital, Rome, Italy, 5 Sant'Eugenio Hospital, Rome, Italy Background: Despite in vitro data showing poor neutralizing activity, clinical efficacy of tixagevimab/cilgavimab (T/C) as pre-exposure prophylaxis (PrEP) in patients (pts) with hematological disease (HD) against the newest omicron

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