Vesatolimod

LOS ANGELES, April 19, 2024 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced the opening of A5374, a phase 1/2a study evaluating the safety, tolerability, and antiviral effect of a novel combination regimen that includes therapeutic T-cell vaccines, two broadly neutralizing antibodies (bNAbs), and an immune-system boosting treatment among people living with HIV who started antiretroviral treatment (ART) during acute (early) HIV infection. A5374 (Triple Immune Strategy for HIV Remission) is a multi-site, randomized, placebo-controlled trial. The study hypothesizes that this combination regimen will be safe and result in a longer period of viral control during a closely monitored pause in ART (known as an analytic treatment interruption) compared to placebo. While current ART can manage HIV very well, it does not cure it and people living with HIV have to take it for the rest of their lives in order to suppress viral replication and protect their immune systems. The approach being studied in A5374 is part of a potential path toward enabling the immune system to manage HIV in the absence of ART for weeks or months. “We expect that controlling HIV in the absence of ART will require a combination of novel treatments to decrease the number of cells harboring HIV and simultaneously stimulate the immune system to keep the virus from replicating,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California Los Angeles. “A5374 is a pivotal trial and we are hopeful that it will provide us with important insights into how to boost the immune system so that it can control HIV.” A5374 will enroll 45 participants aged 18 years and older who started combination ART within 28 days of acute HIV diagnosis (30 who will receive active study treatment and 15 who will receive placebo). The study will last up to approximately two years for each participant. After enrollment, participants will continue taking their HIV medications and will either receive a series of novel treatments or placebo. The novel regimen includes a T-cell vaccine regimen (vaccines vectored by replication-deficient chimpanzee adenovirus ChAdOx1 and poxvirus MVA, each containing six small fragments of HIV); broadly neutralizing antibodies (teropavimab, also known as GS-5423 or 3BNC117-LS, and zinlirvimab, also known as GS-2872 or 10-1074-LS); and vesatolimod (a toll-like receptor 7 or TLR7 agonist, which acts as an immune booster). After about 16 months in the study, participants will stop taking ART. They will be closely monitored for increases in HIV viral load, decreases in CD4 T-cell counts, and symptoms, and will resume taking ART if there is a signal that HIV is rebounding or if they become pregnant. The study will compare the length of time that participants in the active treatment and placebo groups experience viral control while they are off ART. “Our goal with this study is to demonstrate that enhancing immune responses to HIV will lead to sustained suppression of HIV during treatment interruption,” said A5374 Protocol Chair Sharon A. Riddler, M.D., M.P.H., University of Pittsburgh. Carefully monitored analytic treatment interruptions are an important part of HIV cure clinical trials. They can help determine whether a research intervention can reduce latent HIV (HIV that is “hidden” in different cells and tissues but not replicating) or increase immune function and delay or prevent latent HIV from actively replicating. A5374 will take place at up to 10 sites in the United States and Brazil. It is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (which also funds ACTG), under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. The University of Oxford is supplying the T-cell vaccines and conducting endpoint assays. Gilead Sciences is supplying the bNAbs and TLR7 agonist. A5374 is led by Dr. Riddler and Cynthia L. Gay, M.D., M.P.H., University of North Carolina (UNC) (Co-vice Chair) and John Mellors, M.D., University of Pittsburgh (Co-vice Chair). ACTG is led by Dr. Currier and Joseph J. Eron, M.D., UNC (ACTG Vice-Chair). For more information about A5374, please visit clinicaltrials.gov. About ACTG ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH. Media Contact: Jenna Conley, ACTG jenna@conleycommunications.net

- Key Findings from HIV Treatment Research Studies Evaluating Biktarvy® and Investigational Long-Acting Combination Regimens Affirm Commitment to Continuous Biomedical Innovation – – Latest Real-World Evidence Analyses Evaluate Impact of Veklury® on Mortality and Long-COVID – – New Data Evaluating the Safety and Efficacy of Hepcludex® in People with HIV/HBV/HDV Coinfection to Be Presented – FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced the upcoming presentation of new clinical data and real-world evidence (RWE) from its antiviral research and development programs at the 31st Conference on Retroviruses and Opportunistic Infections (CROI 2024) taking place from March 3-6. The data from nearly eighty studies across HIV, COVID-19 and viral hepatitis include late-breaking data, four oral presentations, and reflect Gilead’s commitment to address the evolving needs of a diverse range of people and communities affected by some of the world’s most challenging viruses. “At CROI 2024, we look forward to sharing new research that highlights the breadth of our antiviral portfolio and expanding pipeline as we strive to treat, prevent, cure and help eradicate viral diseases worldwide,” said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “The data selected for presentation at CROI is a reflection of our unwavering commitment to advancing person-centered biomedical innovation in virology, aimed at fulfilling urgent global needs.” HIV Treatment Research Scientific discovery in HIV treatment is a pillar of Gilead’s commitment to help end the epidemic. At CROI 2024, presented study results and analyses will include further evaluation of Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) as a long-term treatment option for a broad range of people with HIV who may also have common comorbidities and other specific health needs. Outcomes from pipeline research studies will also provide insights into investigational treatment candidates, including the novel combination regimen of lenacapavir plus bictegravir. Additionally, key findings from a study evaluating the investigational combination of lenacapavir with broadly neutralizing antibodies (bNAbs) will be featured in a late-breaker oral presentation. A late-breaker oral presentation of Week 24 data from the ongoing Phase 2 study evaluating an investigational once-weekly oral combination regimen of islatravir and lenacapavir will also be presented. Specifically, Biktarvy presentations will include a two-year analysis of data from the Phase 3 ALLIANCE trial evaluating factors associated with hepatitis B (HBV) treatment response in adults with HIV-1/HBV co-infection initiating treatment. Additionally, a late-breaker oral presentation of Week 24 data from the INSIGHT trial evaluating Biktarvy in people with HIV and tuberculosis will be presented. Gilead will also present outcomes from the ARTISTRY-1 Phase 2/3 study investigating the efficacy and safety of switching from a complex stable baseline regimen to an investigational once-daily single-tablet regimen of lenacapavir and bictegravir. Additional lenacapavir data presented at CROI 2024 will evaluate the efficacy and safety of the novel antiviral agent in combination with broadly neutralizing antibodies teropavimab (GS-5423) and zinlirvimab (GS-2872) as a potential long-acting treatment regimen with twice-yearly dosing. Additional HIV treatment research pipeline findings include an oral presentation of new proof-of-concept data on GS-1720, a novel once-weekly integrase strand transfer inhibitor (INSTI) and PRESTIGIO registry data evaluating sensitivity to broadly neutralizing antibodies teropavimab (GS-5423) and zinlirvimab (GS-2872) in people with multi-drug resistant HIV. COVID-19 Research Gilead remains committed to understanding the COVID-19 treatment landscape and will present multiple RWE analyses, including on the impact of Veklury® (remdesivir) in reducing mortality in immunocompromised people hospitalized for COVID-19 during the Omicron period (Dec’21 - April’23). Gilead will also present a study on the disparities in COVID-19 treatment initiation by race and ethnicity among hospitalized patients and one on the effect of Veklury on long-COVID among people hospitalized with COVID-19. Additional presentations will include RWE of Veklury in combination with dexamethasone for the treatment of COVID-19, and study results from kidney transplant patients hospitalized with COVID-19. Viral Hepatitis Research Gilead will present new data evaluating the safety and efficacy of Hepcludex® (bulevirtide) in people living with the coinfections of HIV, hepatitis B (HBV) and hepatitis delta (HDV). The aim of this 96-week analysis from the Phase 3 MYR301 study is to evaluate the safety and efficacy of Hepcludex (2 mg or 10 mg) in patients with HIV/HBV/HDV coinfection. A separate analysis of RWE will examine liver-related events in people living with HIV/HBV coinfection with and without HDV. Since limited data is available to describe the natural history of triple infection with HBV/HIV/HDV, this retrospective cohort study, conducted using HealthVerity claims data from the US, evaluates baseline liver health, HDV prevalence, and the risk of liver-related events in individuals with HBV/HIV with or without HDV. Select accepted abstracts are as follows: HIV Treatment Research (B/F/TAF) Disposition Factors associated with HBV response to B/F/TAF vs. DTG + F/TDF at W96 in people with HIV-1 and HBV Poster Efficacy, safety and PK of BIC/FTC/TAF in adults with HIV and Tuberculosis on rifampicin at Week 24 LB Oral Inflammatory pro B/F/TAF, DTG/ABC/3TC, and DTG+F/TAF over 5-years and effects of viral blips Poster Longitudinal analysis of preexisting resistance-associated mutations prior to B/F/TAF switch Poster Safety of tenofovir alafenamide in individuals with a history of proximal renal tubulopathy on TDF Poster Weight gain in people with HIV (PWH) vs people without HIV (PWoH) over a 3-year period Poster A randomized trial switching adults ≥ 60 years old from first-line ART to B/F/TAF: week 48 results Poster Long-Acting HIV Treatment Research (Lenacapavir) Efficacy and safety of weekly islatravir plus lenacapavir in PWH at 24 weeks: a Phase 2 study LB Oral Lenacapavir efficacy in CAPELLA patients with no fully active agents in optimized background regimen Poster Lenacapavir plus bNAbs for people with HIV and sensitivity to either teropavimab or zinlirvimab Oral HIV Pipeline Research Phase 2 study of switch to daily BIC + LEN in individuals on a multi-tablet HIV treatment regimen Poster Preclinical characterization of GS-5894, a potent NNRTI with once-weekly oral dosing potential Poster Antiviral activity, safety, and pharmacokinetics of GS-1720, a novel weekly oral INSTI Oral Teropavimab and zinlirvimab sensitivity in people living with MDR HIV-1: PRESTIGIO registry data Poster Type I IFN signaling and regulation in vesatolimod-treated virally suppressed adults with HIV-1 Poster HIV Prevention Research Sexual health outcomes among daily and on-demand oral PrEP users in China Oral HIV Cure Research Immune pro ATI in AELIX-002 HTI vaccine trial and its role in post-intervention control Oral COVID-19 Research Remdesivir reduces mortality in immunocompromised patients hospitalized for COVID-19 during Omicron LB Poster Effect of remdesivir on post-COVID conditions among individuals hospitalized with COVID-19 by age LB Poster Disparities in treatment initiation by race and ethnicity among patients hospitalized for COVID-19 Poster Remdesivir+dexamethasone vs. dexamethasone for the treatment of COVID-19: real-world study in the US LB Poster Characteristics and outcomes of kidney transplant patients hospitalized for COVID-19 in the United States Poster Viral Hepatitis Research Risk of liver-related events in individuals with HBV/HIV coinfection with and without HDV Poster Efficacy and safety of BLV 2 or 10 mg for 96 weeks in CHD including two patients with HIV/HBV/HDV Poster For more information, including a complete list of abstracts and their corresponding oral and poster sessions, please visit . Teropavimab, zinlirvimab, vesatolimod, GS-5894 and GS-1720 are investigational compounds, and alone or in combination with lenacapavir, are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use. Their safety and efficacy are unknown. Lenacapavir, marketed as Sunlenca®, is approved in Australia, Canada, the European Union, Israel, Japan, Switzerland, the United Arab Emirates, the United Kingdom and the United States for the treatment of people with multi-drug resistant HIV in combination with other antiretroviral(s). Lenacapavir is being studied in multiple ongoing early and late-stage development programs and has the potential to offer a diverse set of person-centric options for treatment and prevention that could uniquely fit into the lives of people living with HIV and people who would benefit from pre-exposure prophylaxis (PrEP). The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program. Islatravir, alone or in combination with lenacapavir, is investigational and not approved anywhere globally. Their safety and efficacy have not been established. Bictegravir is an investigational compound and is not approved by any regulatory authority for use as a single-agent; its safety and efficacy are not established. ​ Bictegravir and lenacapavir in combination are investigational and not approved anywhere globally. Their safety and efficacy have not yet been established. The use of Biktarvy in individuals with HIV-1/HBV co-infection is investigational, and the safety and efficacy of Biktarvy for this use have not been established. Hepcludex (bulevirtide) has received full marketing authorization from the European Commission for the treatment of adults with chronic HDV and compensated liver disease. In the United States and other areas outside of the European Union and European Economic Area, bulevirtide is an investigational product and its safety and efficacy have not been established. Please see below for the U.S. Indication and Important Safety Information for Veklury and Sunlenca®. Please also see below for U.S. Indication and Important Safety Information, including Boxed Warning, for Biktarvy. There is currently no cure for HIV or AIDS. About Biktarvy Biktarvy is a complete HIV treatment that combines three powerful medicines to form the smallest 3-drug, integrase strand transfer inhibitor (INSTI)-based single-tablet regimen (STR) available, offering simple once-daily dosing with or without food, with a limited drug interaction potential and a high barrier to resistance. Biktarvy combines the novel, unboosted INSTI bictegravir, with the Descovy® (emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, F/TAF) backbone. Biktarvy is a complete STR and should not be taken with other HIV medicines. About Sunlenca Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)] is a first-in-class, long-acting HIV capsid inhibitor for the treatment of HIV-1 infection, in combination with other antiretroviral(s), in adults with multi-drug resistant HIV who are heavily treatment-experienced. Sunlenca is the only HIV treatment option administered twice-yearly. Sunlenca tablets are approved for oral loading during initiation of Sunlenca treatment, prior to or at the time of the first long-acting lenacapavir injection depending on initiation option. The multi-stage mechanism of action of Sunlenca’s active pharmaceutical agent, lenacapavir, is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, Sunlenca is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead's HIV prevention and treatment research program. Lenacapavir for HIV prevention is investigational, and its safety and efficacy for this use have not been established. Lenacapavir is being developed as a foundation for potential future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono agent, that help address individual needs and preferences of people and communities affected by HIV. About Veklury Veklury (remdesivir) is a nucleotide analog prodrug invented by Gilead, building on more than a decade of the company’s antiviral research. Veklury is the antiviral standard of care for the treatment of hospitalized patients with COVID-19 and is a recommended treatment for reducing disease progression in non-hospitalized patients at high risk of disease progression. Veklury has an established safety pro limited known drug interactions in diverse populations. It plays an important role in reducing disease progression across a spectrum of disease severity and enabling patients to recover faster. Veklury is contraindicated in patients with a history of clinically significant hypersensitivity reactions to Veklury or any of its components. Please see below for the U.S. Indication and Important Safety Information for Veklury. Veklury directly inhibits viral replication inside of the cell by targeting the SARS-CoV-2 viral RNA polymerase. Based on in vitro analyses, Veklury retains antiviral activity against recent Omicron subvariants of concern, including XBB, XBB.1.5 and CH.1.1. Veklury continues to be evaluated against emerging variants of interest and concern, including EG.5, EG.5.1 and BA.2.86. Veklury is approved in more than 50 countries worldwide. To date, Veklury and generic remdesivir have been made available to more than 14 million patients around the world, including more than 8 million people in middle- and low-income countries through Gilead’s voluntary licensing program. U.S. Indication for Biktarvy Biktarvy is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy. U.S. Important Safety Information for Biktarvy BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted. Contraindications Coadministration: Do not use BIKTARVY with dofetilide or rifampin. Warnings and precautions Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions. Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported. New onset or worsening renal impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)–containing products. Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min except in virologically suppressed adults <15 mL/min who are receiving chronic hemodialysis. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus. Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations. Adverse reactions Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%). Drug interactions Prescribing information: Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments. Enzymes/transporters: Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1. Drugs affecting renal function: Coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions. Dosage and administration Dosage: Adult and pediatric patients weighing ≥25 kg: 1 tablet containing 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), and 25 mg tenofovir alafenamide (TAF) taken once daily with or without food. Pediatric patients weighing ≥14 kg to <25 kg: 1 tablet containing 30 mg BIC, 120 mg FTC, and 15 mg TAF taken once daily with or without food. For children unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are ingested within approximately 10 minutes. Renal impairment: For patients weighing ≥25 kg, not recommended in patients with CrCl 15 to <30 mL/min, or <15 mL/min who are not receiving chronic hemodialysis, or <15 mL/min who are receiving chronic hemodialysis and have no antiretroviral treatment history. For patients weighing ≥14 kg to <25 kg, not recommended in patients with CrCl <30 mL/min. Hepatic impairment: Not recommended in patients with severe hepatic impairment. Prior to or when initiating: Test patients for HBV infection. Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus. Pregnancy and lactation Pregnancy: There is insufficient human data on the use of BIKTARVY during pregnancy. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects. Discuss the benefit-risk of using BIKTARVY during pregnancy and conception. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population. Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission. U.S. Indication for Sunlenca Sunlenca, a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations. U.S. Important Safety Information for Sunlenca Contraindications Coadministration: Concomitant administration of Sunlenca is contraindicated with strong CYP3A inducers. Warnings and precautions Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported in patients treated with combination antiretroviral (ARV) therapy. Long-acting properties and potential associated risks with Sunlenca: Residual concentrations of Sunlenca may remain in the systemic circulation of patients for up to 12 months or longer. Sunlenca may increase exposure, and potential risk of adverse reactions, to drugs primarily metabolized by CYP3A initiated within 9 months after last injection. Counsel patients regarding the dosing schedule because nonadherence could lead to loss of virologic response and development of resistance. If virologic failure occurs, switch to an alternative regimen if possible. If discontinuing Sunlenca, begin alternate suppressive ARV regimen within 28 weeks from last injection. Injection site reactions may occur, and nodules and indurations may be persistent. Adverse reactions Most common adverse reactions (incidence ≥3%, all grades) are injection site reactions (65%) and nausea (4%). Drug interactions Prescribing information: Consult the full prescribing information for Sunlenca for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments. Enzymes/transporters: Drugs that are strong or moderate inducers of CYP3A may significantly decrease the concentration of Sunlenca. Drugs that strongly inhibit CYP3A, P-gp, and UGT1A1 together may significantly increase the concentration of Sunlenca. Sunlenca may increase the exposure of drugs primarily metabolized by CYP3A, when initiated within 9 months after the last injection of Sunlenca, which may increase the potential risk of adverse reactions. Dosage and administration Dosage: Initiation with 1 of 2 options, followed by maintenance dosing once every 6 months. Tablets may be taken with or without food. Initiation Option 1: Day 1: 927 mg by subcutaneous injection and 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally (2 x 300-mg tablets). Initiation Option 2: Day 1: 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally (2 x 300-mg tablets). Day 8: 300 mg orally (1 x 300-mg tablet). Day 15: 927 mg by subcutaneous injection. Maintenance: 927 mg by subcutaneous injection every 26 weeks +/- 2 weeks from date of last injection. Missed Dose: During the maintenance period, if more than 28 weeks have elapsed since the last injection and if clinically appropriate to continue Sunlenca treatment, restart the initiation dosage regimen from Day 1, Option 1 or Option 2. Pregnancy and lactation Pregnancy: There is insufficient human data on the use of Sunlenca during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established. Lactation: Individuals infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission. U.S. Indication for Veklury Veklury (remdesivir 100 mg for injection) is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg) who are: Hospitalized, or Not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death. For more information, please see the U.S. full Prescribing Information available at . U.S. Important Safety Information for Veklury Contraindication Veklury is contraindicated in patients with a history of clinically significant hypersensitivity reactions to Veklury or any of its components. Warnings and precautions Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of Veklury; most occurred within one hour. Monitor patients during infusion and observe for at least one hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time up to 120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue Veklury and initiate appropriate treatment (see Contraindications). Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received Veklury; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing Veklury if ALT levels increase to >10x ULN. Discontinue Veklury if ALT elevation is accompanied by signs or symptoms of liver inflammation. Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of Veklury with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in antiviral activity of Veklury. Adverse reactions The most common adverse reaction (≥5% all grades) was nausea. The most common lab abnormalities (≥5% all grades) were increases in ALT and AST. Drug interactions Drug interaction trials of Veklury and other concomitant medications have not been conducted in humans. Dosage and administration Administration should take place under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible. Treatment duration: For patients who are hospitalized, Veklury should be initiated as soon as possible after diagnosis of symptomatic COVID-19. For patients who are hospitalized and do not require invasive mechanical ventilation and/or ECMO, the recommended treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended up to 5 additional days, for a total treatment duration of up to 10 days. For patients who are hospitalized and require invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days. For patients who are not hospitalized, diagnosed with mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death, the recommended total treatment duration is 3 days. Veklury should be initiated as soon as possible after diagnosis of symptomatic COVID-19 and within 7 days of symptom onset for outpatient use. Testing prior to and during treatment: Perform hepatic laboratory, and prothrombin time testing prior to initiating Veklury and during use as clinically appropriate. Renal impairment: No dose adjustment of Veklury is recommended in patients with any degree of renal impairment, including patients on dialysis. Veklury may be administered without regard to the timing of dialysis. Pregnancy and lactation Pregnancy: A pregnancy registry has been established for Veklury. Available clinical trial data for Veklury in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes following second- and third-trimester exposure. There are insufficient data to evaluate the risk of Veklury exposure during the first trimester. Maternal and fetal risks are associated with untreated COVID-19 in pregnancy. Lactation: Veklury can pass into breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Veklury and any potential adverse effects on the breastfed child from Veklury or from an underlying maternal condition. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. About Gilead Sciences in Virology Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Gilead has a long history in virology and has pioneered inventions once thought impossible, including antiviral treatments for people and communities affected by some of the most challenging public health concerns including HIV, viral hepatitis and COVID-19. Gilead helps people and communities across the full continuum of care in virology by developing bold advances that treat, prevent and cure viral diseases and collaborating with community and research partners around the world. Gilead is deploying decades of antiviral expertise to provide solutions that help address the unmet and evolving needs of those impacted by viral diseases. Our work in virology has helped to transform the global health landscape and we are committed to advancing person-centered science and actionable education programs that make a difference for people and communities affected by viral diseases. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Biktarvy, Hepcludex, Veklury, lenacapavir, teropavimab, vesatolimod, zinlirvimab, GS-1720 and GS-5894; uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for indications currently under evaluation; the possibility that Gilead may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. U.S. full Prescribing Information for Biktarvy, including BOXED WARNING, U.S. full Prescribing Information for Sunlenca, and U.S. full Prescribing Information for Veklury are available at . Biktarvy, Sunlenca, Veklury, Hepcludex, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. All other trademarks are the property of their respective owner(s). For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter ( @Gilead Sciences ) and LinkedIn, or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.