previously treated with tixagevimab 150 mg plus cilgavimab 150 mg. Simulations based on population PK models suggest that administering an additional dose of tixagevimab 150 mg plus cilgavimab 150 mg ≤3 months after the initial dose will allow a patient to achieve drug concentrations approximating those observed in people who received tixagevimab 300 mg plus cilgavimab 300 mg as their initial dose. For patients who initially received tixagevimab 150 mg plus cilgavimab 150 mg >3 months ago, the simulations suggest that a repeat dose of tixagevimab 300 mg plus cilgavimab 300 mg is necessary. Recommendations Factoring in the limitations outlined above: • The Panel recommends using tixagevimab 300 mg plus cilgavimab 300 mg administered as 2 consecutive 3-mL intramuscular (IM) injections (BIII) as SARS-CoV-2 PrEP for adults and adolescents (aged ≥12 years and weighing ≥40 kg) who do not have SARS-CoV-2 infection, who have not been recently exposed to an individual with SARS-CoV-2 infection, who have not previously received this regimen, AND who: • Are moderately to severely immunocompromised and may have an inadequate immune response to COVID-19 vaccination; or • Are not able to be fully vaccinated with any available COVID-19 vaccines due to a history of severe adverse reactions to a COVID-19 vaccine or any of its components. • The FDA EUA states that individuals who received tixagevimab 150 mg plus cilgavimab 150 mg should be given a second dose as soon as possible. The specific dose of tixagevimab plus cilgavimab that an individual should receive depends on the amount of time that has passed since the first dose was administered: • If the initial dose was administered ≤3 months prior, the second dose should be tixagevimab 150 mg plus cilgavimab 150 mg. • If initial dose was administered >3 months prior, the second dose should be tixagevimab 300 mg plus cilgavimab 300 mg. • Tixagevimab plus cilgavimab is not a substitute for COVID-19 vaccination and should not be used in unvaccinated individuals for whom COVID-19 vaccination is recommended. Individuals who qualify as having moderate to severe immunocompromising conditions under the FDA EUA for tixagevimab plus cilgavimab are those who: • Are receiving active treatment for solid tumors and hematologic malignancies. • Received a solid organ transplant and are receiving immunosuppressive therapy. • Received chimeric antigen receptor T cell therapy or a hematopoietic stem cell transplant (within 2 years of transplantation or receiving immunosuppression therapy). • Have a moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome). • Have advanced or untreated HIV infection (defined as people with HIV and CD4 T lymphocyte Downloaded from https://www.covid19treatmentguidelines.nih.gov/ on 7/6/2022 COVID-19 Treatment Guidelines 27 counts < 0.001). A post hoc analysis after a median follow-up period of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8% to 91.4%) for symptomatic infection in the tixagevimab plus cilgavimab arm. Five cases of COVID-19 were considered to be severe or critical, and 2 COVID-19–related deaths were reported. All of these events occurred in participants who received placebo. Downloaded from https://www.covid19treatmentguidelines.nih.gov/ on 7/6/2022 COVID-19 Treatment Guidelines 28 Adverse events were reported for 35.3% of participants in the tixagevimab plus cilgavimab arm and 34.2% of participants in the placebo arm. Serious adverse events were reported in 1% of participants in each arm; 1 participant in the tixagevimab plus cilgavimab arm had an anaphylactic reaction that was resolved with epinephrine therapy. The incidence of adverse events was similar in both study arms; most events were mild (62%) or moderate (32%). Rare, serious cardiac adverse events occurred in 0.7% of participants in the tixagevimab plus cilgavimab arm and in 0.3% of participants in the placebo arm. All participants who experienced a cardiac event had cardiac risk factors or a history of cardiac disease at baseline. There was no clear temporal pattern between these serious cardiac adverse events and administration of the anti-SARS-CoV-2 mAbs.20 TACKLE was a Phase 3 trial that evaluated the use of tixagevimab plus cilgavimab for the treatment of nonhospitalized patients with mild to moderate COVID-19. In this study, 452 high-risk adults aged ≥18 years received a single IM dose of tixagevimab 300 mg plus cilgavimab 300 mg and had a follow-up visit within 183 days (the median follow-up period was 84 days). Adverse events were reported for 29% of participants in the tixagevimab plus cilgavimab arm and for 36% of participants in the placebo arm; the majority of events were mild to moderate in severity. Serious cardiac adverse events were reported for 4 participants; 3 had received tixagevimab plus cilgavimab and 1 had received placebo. All events occurred in participants who had cardiac risk factors or a history of cardiovascular disease.20 Other Drugs for Pre-Exposure Prophylaxis • The Panel recommends against the use of any oral drugs for SARS-CoV-2 PrEP, except in a clinical trial (AIII). Clinical trials are investigating several agents, including emtricitabine plus tenofovir