MK-8527

默沙东将在EACS 2025发布其HIV治疗和预防管线研究进展 美国新泽西州罗威市，2025年10月9日——默沙东（默沙东是美国新泽西州罗威市默克公司的公司商号）宣布，公司将在2025年10月15日至18日在法国巴黎举行的第20届欧洲艾滋病大会（EACS 2025）上展示其HIV治疗和预防管线的最新研究进展。届时，默沙东将发布的研究进展包括： - 展示Ⅲ期临床试验（MK-8591A-052）第48周的体重与身体成分数据的口头报告，该研究比较两种用于已实现病毒学抑制的HIV-1感染成人的每日一次抗逆转录病毒治疗方案：多拉韦林/islatravir[1]（DOR/ISL，100 mg/0.25mg）及bictegravir/emtricitabine/tenofovir alafenamide（BIC/FTC/TAF, 50mg/200mg/25mg）。 - 展示两项Ⅲ期临床试验第48周空腹血脂和胰岛素抵抗数据的壁报，比较用于已实现病毒学抑制的HIV-1感染成人的每日一次抗逆转录病毒治疗方案：比较DOR/ISL与基线抗逆转录病毒治疗方案的MK-8591A-051研究，以及比较DOR/ISL与BIC/FTC/TAF的MK-8591A-052研究。 - 展示Ⅱ期临床试验（NCT05052996）第96周的安全性和药代动力学数据的口头报告，该研究评估每周一次口服islatravir联合lenacapavir[2]用药方案（MK-8591D）在已实现病毒学抑制且正在接受BIC/FTC/TAF治疗的HIV-1感染成人的效果。 - 展示MK-8527[3]Ⅰ期临床试验（MK-8527-008）安全性和药代动力学数据的壁报，研究对象为中度或重度肾功能受损的成人。MK-8527是默沙东正在研发的每月一次口服HIV暴露前预防用药（PrEP）试验性药物。 Luisa Stamm博士 默沙东实验室副总裁 HIV负责人 “ 我们很高兴能在EACS 2025分享来自HIV研究领域的最新结果，包括对每日一次两药方案DOR/ISL Ⅲ期临床项目的进一步分析，该方案正在接受美国食品药品监督管理局审评。 通过开发每日、每周和每月的口服方案，我们希望能够为感染或受HIV影响的人提供更多元化的治疗和预防选择。 ” 将在EACS 2025公布的部分摘要包括： 摘要标题及作者 日期 HIV治疗 Weight and Body Composition After Switch to Doravirine/Islatravir (100mg/0.25mg) Once Daily from BIC/FTC/TAF in Adults Living With HIV-1: Week 48 Results from a Randomized, Double-Blind Phase 3 Study. Orkin, C, et al. Oral Presentation Thursday, October 16, 2025, 11:00 - 12:00 Evaluation of Fasting Lipids and Insulin Resistance After Switch to Doravirine/Islatravir (100mg/0.25mg) Once Daily: Week 48 Results From Two Randomized Phase 3 Studies in Adults Living With HIV‑1. Calmy, A, et al. Moderated ePoster Friday, October 17, 2025, 15:35 - 16:10 Oral Weekly Islatravir Plus Lenacapavir in Virologically Suppressed People with HIV-1: 96 Week Outcomes from a Phase 2 Study. Colson, A, et al. Oral Presentation Saturday, October 18, 2025， 09:15 - 10:15 Patient-Reported Outcomes From People With HIV-1 Receiving Once-Weekly Oral Islatravir in Combination With Lenacapavir: Phase 2 Week 48 Results. Eron, J, et al. ePoster HIV预防 Pharmacokinetics and Safety of MK-8527 in Adults With Moderate or Severe Renal Impairment, Carstens, R, et al. ePoster EACS 2025期间，默沙东将举办两场专题研讨会，向所有注册参会者开放：政策研讨会“遏制欧洲艾滋病流行：政策挑战与机遇”，10月16日（星期四）18:00–19:30（中欧夏令时，CEST）；医学研讨会“HIV治疗管理优化”，10月17日（星期五）12:30–14:00（中欧夏令时，CEST）。 关于默沙东在HIV领域的承诺 默沙东在HIV领域已有超过35年的持续投入，致力于通过科学研发进展与突破帮助改变HIV治疗格局。我们以创新引领多种药物类别的研发并帮助那些受到HIV影响的人。目前，我们正在开发一系列抗病毒药物，旨在帮助人们管理和预防HIV，以期减少全球范围内不断增加的感染负担。我们希望人们的生活不再被HIV所限，并持续通过变革性创新、全球HIV社群合作、以及提升可及性等多重努力，助力终结HIV流行的目标。 如需了解默沙东HIV治疗和预防临床研究进展的更多信息，请点击阅读原文。 [1] 截至目前，多拉韦林/islatravir尚未获中国国家药品监督管理局（NMPA）的批准 [2] 截至目前，lenacapavir尚未获NMPA的批准 [3] 截至目前，MK-8527尚未获NMPA的批准 若您想了解更多有关疾病知识的信息，请咨询医疗卫生专业人士 10-2025-CN-DOR-00343 关于默沙东 在默沙东（默沙东是美国新泽西州罗威市默克公司的公司商号），我们齐心协力追求共同的目标：我们发挥前沿科学的力量，在全球范围内拯救生命、改善生活。130多年来，我们通过研发重要药物和疫苗，为全人类带来希望。我们致力成为顶尖的研究密集型生物制药公司——当下，我们正处于研发前线，推出创新解决方案，以推进人类和动物疾病的预防和治疗。我们建立了一个多元、包容的全球员工体系，以负责的态度经营每一天，确保所有人、所有社区都能有一个安全、可持续和健康的未来。更多信息，请访问www.msd.com，并在X（前身为Twitter）、LinkedIn和Youtube平台关注我们。 关于默沙东中国 中国是默沙东全球增长战略中至关重要的一部分。默沙东中国总部设在上海，同时在北京设有研发中心、在杭州、宁波和天津分别设有工厂，实现了研发、制造和商业运营三擎合一。我们全心全意，向中国大众提供高质量的创新药物、疫苗和服务，造福中国社会。更多信息，敬请访问默沙东中国官网，或关注默沙东中国在微信上的官方社交媒体账号。 默沙东前瞻性声明 默沙东是美国新泽西州罗威市默克公司的公司商号（下称“公司”）。本新闻稿包含根据《1995 年美国私人证券诉讼改革法案》之安全条款而做出的“前瞻性声明”。本文内容基于公司管理层当前的看法和预期，并且受制于可能出现的重大风险和不确定因素。默沙东不保证在研产品能获得所需的监管部门批准或取得商业成功。如果相关假设与现实有所出入、出现风险，或发生不确定情况，实际结果可与前瞻性声明中的预期有实质上的差异。 风险和不确定因素包括但不仅限于一般行业情况与竞争、一般经济因素（包括利率与汇率浮动）、美国及其他国家制药行业监管以及医疗政策的影响、全球范围内控制医疗成本的趋势、技术发展、竞争对手获得的新产品与专利、新产品开发固有的挑战（包括获得监管部门批准）、默沙东对未来市场形势做出准确预测的能力、生产上的困难或迟延、国际经济金融状况不稳定与主权风险、对默沙东专利和其它创新产品保护的有效性的依赖程度，以及公司面临专利诉讼和/或监管行动的风险。 默沙东没有义务就新信息、未来事件或其它原因对任何前瞻性声明进行公开的更新。尚有其它因素可能导致实际结果与前瞻性声明存在实质性差异，请参见默沙东2024年年报10-K报表以及公司在美国证券交易所备案的其它文件（可在美国证券交易所网站www.sec.gov上查阅）。

RAHWAY, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today the presentation of additional data from the Phase 3 studies of the investigational, once-daily, oral, two-drug regimen of doravirine/islatravir [DOR/ISL (100mg/0.25mg)] in adults with HIV-1 infection that was virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamidei [BIC/FTC/TAF (50 mg/200 mg/25 mg)] in trial MK-8591A-052 or antiretroviral therapy [baseline antiretroviral therapy (bART)] in trial MK-8591A-051. These additional findings will be shared at the 20th European AIDS Conference being held in Paris and follow positive Phase 3 data presented at CROI 2025, which showed that the investigational two-drug regimen of DOR/ISL maintained viral suppression and demonstrated non-inferiority to the three-drug regimen BIC/FTC/TAF in MK-8591A-052 and baseline ART in MK-8591A-051, with no observed treatment-emergent resistance to DOR or ISL. In trial MK-8591A-052, adults living with virally suppressed HIV-1 infection who switched to DOR/ISL from BIC/FTC/TAF showed minimal changes in weight and body composition at Week 48 (exploratory endpoints). These changes were comparable to trial participants who continued BIC/FTC/TAF. In both trials, adults who switched to DOR/ISL from their current regimen (BIC/FTC/TAF or bART) saw no clinically meaningful changes in fasting lipids (exploratory endpoint in MK-8591A-052; secondary endpoint in MK-8591A-051) or in the homeostatic model assessment of insulin resistance (HOMA-IR) (exploratory endpoints). These changes were comparable to trial participants who continued on their respective prior antiretroviral therapy, BIC/FTC/TAF or bART. Participants who entered the trials on lipid-lowering therapy were excluded from the fasting lipids analysis. The percentage of participants who modified or initiated lipid-lowering therapy during the study was comparable across the treatment groups. “Weight and body composition are often central concerns for people living with HIV, who may face obesity and other weight-related issues,” said Dr. Chloe Orkin, dean for healthcare transformation, Queen Mary University of London. “The Week 48 results from the Phase 3 DOR/ISL trial (MK-8491A-052) are important to consider because they show minimal and similar changes in weight and body composition from baseline when participants switched to DOR/ISL.” “Comorbid conditions play an important role in the overall care for people living with HIV. Shifts in weight, body composition and lipids can increase the risk of cardiovascular disease and complicate management of other chronic illnesses,” said Dr. Eliav Barr, senior vice president and chief medical officer, Merck Research Laboratories. “We are pleased that these data show that switching to DOR/ISL had minimal impact on weight and body composition and no clinically meaningful impact on fasting lipids in adults with virologically suppressed HIV-1 infection who switched from their current antiretroviral therapy.” In the double-blind trial MK-8591A-052, results for changes in weight and body composition showed that both the mean change and mean percent change in weight from baseline at Week 48 were minimal and similar in both treatment groups (exploratory endpoint): the mean weight change from baseline for the DOR/ISL treatment group was -0.03 kg (95% CI: -0.54, 0.48) vs. +0.28 kg (95% CI: -0.32, 0.88) for the BIC/FTC/TAF group, and the mean percentage weight change from baseline was 0.10% (95% CI: -0.50, 0.69) for DOR/ISL (n=316), compared to 0.39% (95% CI: -0.31, 1.09) for BIC/FTC/TAF (n=163). At Week 48, 14.6% and 3.5% of participants who switched to DOR/ISL experienced a ≥5% and ≥10% weight gain from baseline, respectively, compared with 16.0% and 2.5% of participants who continued BIC/FTC/TAF. Additionally, mean percent changes in lean body mass, peripheral fat and trunk fat and mean changes in body mass index and waist-to-hip ratio were small and comparable between the two treatment groups. Across both trials (MK-8591A-052 and MK-8591A-051), the pooled DOR/ISL group’s mean changes from baseline in fasting lipids, including total cholesterol, HDL, LDL and triglycerides were minimal, with no substantial differences from comparator groups (exploratory endpoint in MK-8591A-052; secondary endpoint in MK-8591A-051). Mean changes in fasting insulin, glucose and HOMA-IR were minimal across groups (exploratory endpoints). The proportion of participants with type 2 diabetes who modified their diabetic medication was <5% across treatment groups. A comparable proportion of participants initiated lipid-lowering therapy (pooled DOR/ISL 4.8%, BIC/FTC/TAF 4.1%, bART 5.9%) across the two trials. Earlier this year, the U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for DOR/ISL and has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA). About the Phase 3 trial MK-8591A-052 MK-8591A-052 is a Phase 3, double-blind, randomized, active-controlled clinical trial to evaluate the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL (100mg/0.25mg) in adults with HIV-1 infection that has been virologically suppressed on BIC/FTC/TAF (50mg/200mg/25mg). The primary efficacy endpoint was the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%). In this trial, 513 adults with HIV-1 who had virologic suppression for three months or more on BIC/FTC/TAF, no history of treatment failure and no known resistance to DOR were randomized (2:1) and switched to DOR/ISL (n=342) or continued treatment with BIC/FTC/TAF (n=171). The median age of participants was 47 years; 21.4% were assigned female sex at birth, 30.8% were Black or African American, and 22.8% were Hispanic or Latine. The median duration of BIC/FTC/TAF treatment prior to trial enrollment was 3.4 years (IQR 2.0-5.0). At Week 48, the mean percent change in total lymphocyte and CD4 counts were similar for DOR/ISL and BIC/FTC/TAF. There were identical rates of discontinuation for protocol-specified decreases in total lymphocyte and/or CD4 counts (two participants (0.6%) in the DOR/ISL group and one participant (0.6%) in the BIC/FTC/TAF group). Drug-related adverse events (AEs) and discontinuations due to drug-related AEs were similar between groups (n=35, 10.2% for DOR/ISL and n=16, 9.4% for BIC/FTC/TAF; n=4, 1.2% for DOR/ISL and n=2, 1.2% for BIC/FTC/TAF, respectively). Rates of toxicity grade 3 or 4 AEs and serious AEs were similar for DOR/ISL and BIC/FTC/TAF (n=25, 7.3% for DOR/ISL and n=13, 7.6% for BIC/FTC/TAF; n=15, 4.4% for DOR/ISL and n=11, 6.4% for BIC/FTC/TAF, respectively). The most common AEs (>6% in either study arm) were arthralgia, COVID-19, nasopharyngitis, and fatigue. One participant on DOR/ISL discontinued due to a drug-related serious AE (immune thrombocytopenia). There were two cases of low-level hepatitis B (HBV) viremia (HBV DNA <50 IU/mL) with no antigenemia or elevated transaminases in the DOR/ISL group and no cases in the BIC/FTC/TAF group; there were no cases of clinical HBV reactivation. About the Phase 3 Trial MK-8591A-051 MK-8591A-051 is a Phase 3, open-label, randomized, active-controlled clinical trial evaluating the efficacy and safety of a switch to investigational, oral, once-daily DOR/ISL (100mg/0.25mg) in adults with HIV-1 infection that have been virologically suppressed using bART. The primary efficacy endpoint was the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%). In this trial, 551 adults with HIV-1 RNA <50 copies/mL for three months or more on oral 2- or 3-drug ART, with no history of treatment failure and no known virologic resistance to DOR, were randomized 2:1 and switched to DOR/ISL (n=366) or continued bART (n=185), stratified by bART regimen. The median age of participants was 51 years; 39.7% were assigned female sex at birth, 45.4% were Black or African American, and 14.5% were Hispanic or Latine. At baseline, 64.2% were treated with an InSTI-based regimen, 30.3% with an NNRTI-based regimen, and 5.4% with a protease inhibitor (PI)-based regimen, with median duration on current ART of 3.8 years (IQR 2.0-6.3). At Week 48, the mean percent change in total lymphocyte and CD4 counts were similar for DOR/ISL and bART. No participants discontinued treatment due to decrease in total lymphocyte and/or CD4 counts. In this open-label study, drug-related AEs were more commonly reported with DOR/ISL (n=44; 12.0%) than bART (n=9; 4.9%). Rates of toxicity grade 3 or 4 AEs and serious AEs were similar for DOR/ISL and bART (n=39, 10.7% for DOR/ISL and n=18, 9.7% for bART and n=23, 6.3% for DOR/ISL and n=9, 4.9% for bART, respectively). There were no drug-related serious AEs and there were no discontinuations due to serious AEs in the DOR/ISL group; there was one drug-related serious AE and two discontinuations due to serious AEs in the bART group. The most common drug-related AEs were diarrhea (DOR/ISL 3.3%, bART 0%), fatigue (1.9%, 0.5%), dizziness (1.9%, 0.5%), abdominal distention (1.6%, 0%), weight increased (1.6%, 0%), and headache (1.6%, 1.1%). There was one case of low-level HBV viremia with no antigenemia or elevated transaminases in the DOR/ISL group and no cases in the bART group; there were no cases of clinical HBV reactivation. About islatravir (MK-8591) and Merck’s HIV research Islatravir (MK-8591), Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination and induction of structural changes in the viral DNA, resulting in delayed chain termination. Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential daily and once-weekly treatments for HIV-1, with islatravir serving as the anchor medicine in the treatment regimens based on its potency and resistance profile. In addition to the MK-8591A-051 and MK-8591A-052 trials, ongoing Phase 3 trials of daily DOR/ISL (100mg /0.25mg) include MK-8591A-053 in people with HIV who had not previously received treatment (treatment-naïve), and MK-8591A-054 evaluating open-label DOR/ISL (100 mg/0.25 mg) in individuals who participated in earlier Phase 3 trials of DOR/ISL (100 mg/0.75 mg). Islatravir in combination with Gilead’s lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1(NCT05052996), and islatravir in combination with our company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2b development (MK-8591B-060) as an oral once-weekly treatment. Merck’s commitment to researching NRTTIs includes MK-8527, an investigational, novel oral, once-monthly NRTTI candidate that is in Phase 3 development for HIV-1 pre-exposure prophylaxis (PrEP). For an overview of Merck’s HIV treatment and prevention clinical development program, please click here. Merck’s commitment to HIV For more than 35 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage their HIV and to help prevent HIV, with the goal of reducing the growing burden of infection worldwide. We want to ensure people are not defined by HIV, and our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at helping to end the HIV epidemic for everyone. Indications and usage for PIFELTRO® (doravirine) and DELSTRIGO® (doravirine, lamivudine, and tenofovir disoproxil fumarate) in the U.S. PIFELTRO is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine. DELSTRIGO is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO. Selected Safety Information Warning: Posttreatment Acute Exacerbation of Hepatitis B Virus (HBV) for DELSTRIGO All patients with HIV-1 should be tested for the presence of HBV before initiating ARV therapy. Severe acute exacerbations of HBV have been reported in people with concomitant HIV-1 and HBV who have discontinued products containing lamivudine or tenofovir disoproxil fumarate (TDF), which are components of DELSTRIGO. Patients coinfected with HIV-1 and HBV who discontinue DELSTRIGO should be monitored with both clinical and laboratory follow-up for at least several months after stopping DELSTRIGO. If appropriate, initiation of anti-HBV therapy may be warranted. Contraindications PIFELTRO and DELSTRIGO are contraindicated when coadministered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John’s wort (Hypericum perforatum)), as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO and PIFELTRO. DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to lamivudine. Warnings and Precautions Severe Skin Reactions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue PIFELTRO or DELSTRIGO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Clinical status should be closely monitored, and appropriate therapy should be initiated. New or Worsening Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. DELSTRIGO should be avoided with concurrent or recent use of a nephrotoxic agent (eg, high-dose or multiple NSAIDs). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in people living with HIV with risk factors for renal dysfunction who appeared stable on TDF. Prior to or when initiating DELSTRIGO, and during treatment, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue DELSTRIGO in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Discontinue DELSTRIGO if estimated creatinine clearance declines below 50 mL/min. Bone Loss and Mineralization Defects In clinical trials in adults living with HIV, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with the use of TDF. The effects of TDF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk in adults are unknown. Immune Reconstitution Syndrome Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment. Drug Interactions Because DELSTRIGO is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Coadministration of PIFELTRO with efavirenz, etravirine, or nevirapine is not recommended. If DELSTRIGO is coadministered with rifabutin, take one tablet of DELSTRIGO once daily, followed by one tablet of doravirine (PIFELTRO) approximately 12 hours after the dose of DELSTRIGO. If PIFELTRO is coadministered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart). Consult the full Prescribing Information prior to and during treatment for more information on potential drug-drug interactions. Dosage and Administration/Specific Populations Renal Impairment Because DELSTRIGO is a fixed-dose combination tablet and the dosage of lamivudine and TDF cannot be adjusted, DELSTRIGO is not recommended in patients with estimated creatinine clearance less than 50 mL/min. Adverse Reactions The most common adverse reactions with DELSTRIGO (incidence ≥5%, all intensities) were dizziness (7%), nausea (5%), and abnormal dreams (5%). The most common adverse reactions with PIFELTRO (incidence ≥5%, all intensities) were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (6%), abdominal pain (5%), and abnormal dreams (5%). By week 96 in DRIVE-FORWARD, 2% of adult participants in the PIFELTRO group and 3% in the darunavir+ritonavir (DRV+r) group had adverse events leading to discontinuation of study medication. By week 96 in DRIVE-AHEAD, 3% of adult participants in the DELSTRIGO group and 7% in the efavirenz (EFV)/emtricitabine (FTC)/TDF group had adverse events leading to discontinuation of study medication. In DRIVE-FORWARD, mean changes from baseline at week 48 in LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were pre-specified. LDL-C: -4.6 mg/dL in the PIFELTRO group vs 9.5 mg/dL in the DRV+r group. Non-HDL-C: -5.4 mg/dL in the PIFELTRO group vs 13.7 mg/dL in the DRV+r group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, mean changes from baseline at week 48 in LDL-C and non-HDL-C were pre-specified. LDL-C: -2.1 mg/dL in the DELSTRIGO group vs 8.3 mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the DELSTRIGO group vs 12.7 mg/dL in the EFV/FTC/TDF group. The clinical benefits of these findings have not been demonstrated. In DRIVE-SHIFT, mean changes from baseline at week 24 in LDL-C and non-HDL-C were pre-specified. LDL-C: -16.3 mg/dL in the DELSTRIGO group vs -2.6 mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL in the DELSTRIGO group vs -2.1 mg/dL in the PI + ritonavir group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, neuropsychiatric adverse events were reported in the three pre-specified categories of sleep disorders and disturbances, dizziness, and altered sensorium. Twelve percent of adult participants in the DELSTRIGO group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DELSTRIGO group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DELSTRIGO group and 8% in the EFV/FTC/TDF group reported altered sensorium. The safety of DELSTRIGO in virologically-suppressed adults was based on week 48 data from participants in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult participants was similar to that in participants with no ARV treatment history. Serum ALT and AST Elevations: In the DRIVE-SHIFT trial, 22% and 16% of participants in the immediate switch group experienced ALT and AST elevations greater than 1.25 X ULN, respectively, through 48 weeks on DELSTRIGO. For these ALT and AST elevations, no apparent patterns with regard to time to onset relative to switch were observed. One percent of participants had ALT or AST elevations greater than 5 X ULN through 48 weeks on DELSTRIGO. The ALT and AST elevations were generally asymptomatic, and not associated with bilirubin elevations. In comparison, 4% and 4% of participants in the delayed switch group experienced ALT and AST elevations of greater than 1.25 X ULN through 24 weeks on their baseline regimen. Pregnancy/Breastfeeding There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO or DELSTRIGO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Inform individuals with HIV-1 infection of the potential risks of breastfeeding, including: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable, and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube, and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). i bictegravir/emtricitabine/tenofovir alafenamide (BIKTARVY) is a registered trademark of Gilead Sciences, Inc.