ABSTRACT
Background: Within the ACTIV-2/A5401 platform (NCT04518410), the safety and efficacy of tixagevimab/cilgavimab (T/C), an anti-SARS-CoV-2 monoclonal antibody combination, was studied in outpatients with COVID-19. Intravenous (IV) and intramuscular (IM) administration of T/C were assessed. Method(s): Non-hospitalized adults >=18 years enrolled within 10 days of positive SARS-CoV-2 test and symptom onset. Participants at higher risk of disease progression were eligible for IV T/C 300mg (150mg each component) or placebo;all were eligible for IM T/C 600mg (300mg each) administered to the lateral thigh or placebo. Co-primary outcomes were: time to symptom improvement through day 28;nasopharyngeal (NP) SARS-CoV-2 RNA below lower limit of quantification (LLoQ) on days 3, 7 or 14;and treatment emergent Grade >=3 adverse events. Result(s): Between February and May 2021, 223 participants (106 T/C, 117 placebo) initiated study intervention and were included in the IM analysis and 114 participants (58 T/C, 56 placebo) in the IV analysis;the IV study was stopped early for administrative reasons. Both studies enrolled 45% Latinx;the IM and IV populations included 12% and 19% Black participants, 49% and 59% female sex at birth, and median age was 39 and 44 years, respectively, all of which were balanced between active vs placebo for each. Median (IQR) days from symptom onset at enrollment was 6 (4, 7). There were no differences in time to symptom improvement comparing IM T/C to placebo (median 8 (IQR 7, 12) vs 10 (8, 13) days;p=0.35) or IV T/C to placebo (11 (9, 15) vs 10 (7, 15) days;p=0.71). A significantly greater proportion (80%) in the IM T/C arm had NP SARS-CoV-2 RNA below LLoQ at day 7 compared to placebo (65%), but not days 3 or 14, overall p=0.003 across visits. Secondary and post-hoc analyses revealed antiviral effects within the smaller IV study. There was no difference in Grade >=3 AEs with either administration route. Fewer participants were hospitalized who received T/C vs placebo (4 vs 7 in IM group;0 vs 4 in IV group), neither group reaching statistical significance. Conclusion(s): Tixagevimab/cilgavimab administered IM or IV was well-tolerated and demonstrated antiviral activity and a trend towards fewer hospitalizations, but did not change time to symptom improvement in mild-to-moderate COVID-19 compared to placebo. Monoclonal antibodies administered intramuscularly to the thigh may present a valuable alternative for early SARSCoV-2 infection. Virologic Outcomes of Tixagevimab/Cilgavimab treatment 600mg IM (panels A and B) or 300mg IV (panels C and D) versus placebo.
ABSTRACT
Background: COVID-19 outcomes among people with HIV (PWH) remain inconclusive. We characterized all cases of COVID-19 identified in a long-term multi-site cohort of PWH, as well as factors associated with increasing severity of COVID-19 during the early months of the COVID-19 pandemic. Methods: We examined all PWH with SARS-CoV-2 infection and COVID-19 disease identified from laboratory testing data (RT-PCR, antigen test results) and ICD-10 codes March-July 2020 from seven sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort. Cases were verified by medical record review. We evaluated predictors of increased disease severity, indicated by hospitalization. Relative risks were estimated using Poisson regression, adjusted for clinical and demographic characteristics using disease risk scores. Results: Among 13,862 PWH in care (20% female, median age 52 (IQR 40-59), 58% Black or Hispanic race/ethnicity), 198 COVID-19 cases were detected during the study period. A higher proportion of PWH with COVID-19 were female (27%), Black or Hispanic (76%), and had BMI ≥30 (45%). No significant differences in CD4+ count (current or lowest) were seen between PWH with and without COVID-19. We found evidence suggesting more unstable housing among COVID-19 cases compared to non-cases (14% vs. 9%). Among PWH with COVID-19, 38 (19%) were hospitalized, 10 (5%) required intensive care, 8 (4%) received invasive mechanical ventilation, and 4 (2%) died. Hospitalization among PWH with COVID-19 was associated with: CD4+ count ≤350 (aRR 1.77;95% CI 1.05, 2.98);age ≥60 (aRR 2.0;95%CI 1.13, 3.54);pre-existing kidney disease with eGFR <60 (aRR 1.76;95% CI 0.99, 3.13);and BMI ≥30 (aRR 1.96;95% CI 1.02, 3.78) (Table). Conclusion: The population frequency of COVID-19 detected in PWH was 1.4%, likely an underestimate of the true frequency of SARS-CoV-2 infection and COVID-19 disease due to evolving testing availability and access over time. A higher proportion of PWH with COVID-19 were Black or Hispanic, in excess of the overrepresentation of people of color with HIV compared to the general population. PWH with decreased eGFR, low CD4+ count, and obesity had greater risk of more severe COVID-19 disease. Our results highlight disparities in risk of COVID-19 acquisition among PWH in the US and indicate additional vigilance in screening and monitoring of COVID-19 among PWH with these characteristics. The expected accrual of additional COVID-19 cases will allow more precise evaluation of the impact of comorbidities. (Figure Presented).