Cobicistat

艾滋病，即获得性免疫缺陷综合征（AIDS），其病原体为人类免疫缺陷病毒（HIV），亦称艾滋病病毒。AIDS是影响公众健康的重要公共卫生问题之一。《中国艾滋病诊疗指南（2024版）》重点对抗病毒治疗、全程管理、机会性感染、人类免疫缺陷病毒（HIV）感染合并肿瘤、HIV感染的预防与干预等内容进行了更新，并新增“艾滋病免疫重建不全（INR）”内容，首次提出了“艾滋病脆弱人群”的概念，增加了诊治推荐意见及其推荐证据和推荐强度。 新版指南包括流行病学、实验室检测、常见机会性感染、抗病毒治疗、免疫重建炎性综合征、INR、HIV母婴垂直传播阻断及单阳家庭生育等内容。 流行病学 推荐意见1 对HIV/AIDS患者的配偶和性伴、与HIV/AIDS患者共用注射器的静脉药物依赖者、HIV/AIDS患者所生子女，以及具有疑似HIV感染高危行为和/或临床症状的临床就诊者，医务人员应主动提供HIV相关检测及相应的咨询服务（C1）。 实验室检测 推荐意见2 HIV筛查试验阳性者需进一步通过补充试验包括抗体补充试验（HIV-1/2抗体确证试验）和核酸补充试验（HIV-1核酸定性和定量检测）来确认HIV感染（A1）。 推荐意见3 初治HIV感染者在启动抗反转录病毒治疗（ART）之前应进行基因型耐药检测。新确诊HIV感染者或使用长效卡替拉韦（CAB-LA）进行PrEP后仍感染HIV的患者，如考虑存在HIV对INSTI耐药，则应进行整合酶基因突变检测（C1）。 诊断标准 推荐意见4 HIV感染的全过程可分3个期，即急性期、无症状期和AIDS期；HIV/AIDS的诊断需结合流行病学史、临床表现和实验室检查结果进行综合分析，慎重做出诊断，并进行临床分期（A1）。 常见机会性感染 肺孢子菌肺炎（PCP） 推荐意见5 PCP的病原治疗首选复方磺胺甲噁唑（SMZ-TMP），甲氧苄啶 （TMP）15～20 mg/（kg·d），磺胺甲噁唑（SMZ）75～100 mg/（kg·d），分3～4次用，疗程为21 d；重症患者（PaO2＜70 mm Hg或肺泡-动脉血氧分压差＞35 mm Hg）早期（72 h内）可应用糖皮质激素（泼尼松或静脉用甲泼尼龙）治疗，激素总疗程为21 d（A1）。 推荐意见6 CD4+T淋巴细胞计数＜200个/μL的HIV/AIDS患者应使用SMZ-TMP预防PCP，一级预防为1片/天，二级预防2片/天；ART后CD4+T淋巴细胞计数增加到＞200个/μL并持续≥3～6个月可停止预防用药（A1）。 结核病 推荐意见7 HIV/AIDS患者在每次就诊时均应系统接受结核病筛查，临床上应注意结合病史、结核病典型症状和体征，以及影像学和实验室检查，系统筛查结核病的可能（B1）。 推荐意见8 HIV/AIDS患者结核病的治疗原则与普通结核病患者相同，但抗结核药物使用时应注意与抗病毒药物之间的相互作用及配伍禁忌（A1）。 推荐意见9 所有合并结核病的HIV/AIDS患者无论CD4+T淋巴细胞计数水平的高低均应尽早接受ART，推荐在抗结核治疗后2周内尽早启动ART。合并耐药结核病，在使用二线抗结核药物后8周内开始ART；对于中枢神经系统结核病患者，通常建议在抗结核后的4～8周启动ART（C1），使用糖皮质激素治疗的AIDS合并结核性脑膜炎的患者，建议在启动抗结核后2周内启动ART（C1）。 活动性结核病或非结核分枝杆菌（NTM）感染 推荐意见10 HIV/AIDS合并NTM感染主要为鸟分枝杆菌（MAC）感染，确诊MAC病有赖于从患者血液、淋巴结、骨髓及其他无菌组织或体液中培养出MAC（A1）。 推荐意见11 MAC病首选病原治疗方案为：克拉霉素500 mg/次，2次/天（或阿奇毒素500 mg/d）+乙胺丁醇15 mg/（kg·d），同时联合应用利福布汀（300～600 mg/d）。严重感染及严重免疫抑制（CD4+T淋巴细胞计数＜50个/μL）患者可加用阿米卡星［10 mg/（kg·d），肌内注射，1次/天］或喹诺酮类抗菌药物如左氧氟沙星或莫西沙星（B1）。疗程通常至少为12个月。抗MAC治疗开始2周后尽快启动ART（B1）。 巨细胞病毒（CMV）感染 推荐意见12 CMV视网膜炎的确诊有赖于检眼镜检查，治疗可选择更昔洛韦、缬更昔洛韦、膦甲酸钠，疗程为2～3周；局部治疗：玻璃体内注射更昔洛韦或膦甲酸，每周重复1次，疗程到视网膜病变被控制、病变不活动为止（A1）。 推荐意见13 不推荐HIV/AIDS患者对CMV感染进行一级预防。二级预防方案推荐首选更昔洛韦（1.0 g，3次/天，口服），在CD4+T淋巴细胞计数＞100个/μL且持续3～6个月以上时可考虑停止二级预防（B1）。 弓形虫脑病 推荐意见14 弓形虫脑病病原治疗首选乙胺嘧啶（负荷剂量为100 mg，口服，2次/天，此后50～75 mg/d维持）+磺胺嘧啶（1～1.5 g，口服，4次/天），替代治疗：SMZ-TMP（3片，每日3次，口服）联合克林霉素（600 mg/次，静脉给药，每6小时1次）或阿奇霉素（0.5 g/d）。疗程至少为6周（A1）。 推荐意见15 对无弓形虫脑病病史但CD4+T淋巴细胞计数＜200个/μL且弓形虫IgG抗体阳性的HIV/AIDS患者应使用SMZ-TMP（2片/次，1次/天）来预防弓形虫脑病（B1）。接受ART后，CD4+T淋巴细胞计数增加到＞200个/μL并持续＞3个月，可停止预防用药（A1）；或ART后CD4+T淋巴细胞计数在100～200个/μL，病毒载量持续低于检测下限3～6个月，也可考虑停止预防用药（B1）。 推荐意见16 对既往患过弓形虫脑病者要长期使用乙胺嘧啶（25～50 mg/d）联合磺胺嘧啶（2～4 g/d）预防，直至CD4+T淋巴细胞计数增加到＞200个/μL并持续≥6个月（A1）。一旦CD4+T淋巴细胞计数下降到＜200个/μL，需重启预防用药（C1）。 真菌感染 推荐意见17 HIV/AIDS合并隐球菌性脑膜炎的病原体治疗分为诱导期、巩固期、维持期3个阶段，诱导期首选两性霉素B［0.5~0.7 mg/(kg·d)］或两性霉素 B 脂质体（L-AMB）［3~4 mg/(kg·d)］+氟胞嘧啶［100 mg/(kg·d)］，诱导期至少4周，巩固期首选氟康唑（600～800 mg/d）治疗至少6周，维持期选择氟康唑（200 mg/d），维持期至少1年，持续至患者通过ART后CD4+T淋巴细胞计数＞100个/μL并持续至少6个月时可停药（A1）。 推荐意见18 HIV/AIDS合并隐球菌性脑膜炎诱导期可首选单次L-AMB 10 mg/kg联合使用2周的氟胞嘧啶［100 mg/(kg·d) ］和氟康唑（600~800 mg/d）进行治疗（A1）。 推荐意见19 HIV/AIDS合并隐球菌性脑膜炎患者正规抗隐球菌治疗4～6周后启动ART (A1)。 推荐意见20 合并隐球菌性抗原血症的HIV/AIDS患者建议给予氟康唑400～800 mg/d口服10周，而后改为200 mg/d口服预防性治疗，总疗程为6～12个月（C1）。 推荐意见21 HIV/AIDS合并马尔尼菲篮状菌病诱导期抗真菌治疗方案首选两性霉素B［0.5～0.7 mg/(kg·d) ］或L-AMB［3～5 mg/(kg·d) ］或两性霉素B胆固醇硫酸酯复合物［3~4 mg/(kg·d) ］，静脉滴注2周（A1）；巩固期为口服伊曲康唑或伏立康唑200 mg，每12小时1次，共10周；随后进行二级预防，口服伊曲康唑200 mg，1次/d（B1），至患者通过ART后CD4+T淋巴细胞计数＞100个/μL，并持续至少6个月可停药（B）。一旦CD4+T淋巴细胞计数＜100个/μL，需要重启预防治疗（C1）。 抗病毒治疗 成人及青少年抗病毒治疗时机与方案 ①成人及青少年启动ART的时机： 推荐意见22 所有HIV感染无论CD4+T淋巴细胞水平高低均建议尽早开始ART，以降低发病率和病死率，并预防HIV传播（B1）；有条件患者建议快速启动ART（确诊后7 d内）或确诊当天启动ART（A1）。 ②成人及青少年初始ART方案： 推荐意见23 成人初治患者推荐ART方案通常由2种核苷类反转录酶抑制剂（NRTI）类骨干药物联合第三类药物组成，第三类药物可以为整合酶链转移抑制剂（INSTI）或非核苷类反转录酶抑制剂（NNRTI）或者增强型蛋白酶抑制剂（PI，含利托那韦或考比司他）；也可以选用复方单片制剂（STR）（A1）；对于HBV表面抗原（HBsAg）阴性、病毒载量＜5×105拷贝/mL的初治患者可首选多替拉韦/拉米夫定的ART方案（A1）。 特殊人群抗病毒治疗 儿童： 推荐意见24 儿童一旦确诊HIV感染，无论CD4+T淋巴细胞水平高低，均建议立即开始ART（B1）。 推荐意见25 儿童初治患者ART方案推荐为2种NRTI类骨干药物联合第三类药物治疗，第三类药物可以为INSTI或NNRTI或者增强型PI（含利托那韦或考比司他）（B1）。 合并结核分枝杆菌感染者： 推荐意见26 HIV/AIDS合并结核病患者推荐首选ART方案为替诺福韦（齐多夫定）+拉米夫定（恩曲他滨）+依非韦伦或多替拉韦（A1），与利福平合用时，多替拉韦的剂量建议加倍（50 mg，2次/天）（A1）。 合并HBV感染者： 推荐意见27 HIV/HBV合并感染者不论CD4+T淋巴细胞计数水平如何，均建议尽早启动ART，ART方案中应包含2种具有抗HBV活性的抗病毒药物，ART骨干药物中的核苷类药物推荐选择替诺福韦（或丙酚替诺福韦[TAF]）+拉米夫定（或恩曲他滨）（B1）。 合并HCV感染者： 推荐意见28 HIV合并HCV感染者应尽早启动ART和积极抗HCV治疗，抗HCV治疗的方案和疗程与单纯HCV感染者相同，应注意与ART药物间的相互作用（A1）。 抗病毒治疗监测 推荐意见29 启动ART后建议每3～6个月进行病毒学、免疫学和临床情况随访以评价ART的疗效，及时发现抗病毒药物的不良反应及是否出现病毒耐药等，以便及时更换药物而保证ART成功（C1）。 药物相互作用 推荐意见30 推荐病毒载量检测作为发现和确认抗病毒治疗失败的首选方法（C1）；一旦确认抗病毒治疗失败，则应尽快进行HIV耐药检测（C1）。 推荐意见31 病毒出现病毒学失败时应首先评估患者的治疗依从性、药物-药物或药物-食物相互作用，尤其服药依从性是治疗成败的决定因素。ART失败的患者应根据HIV耐药检测结果来进行ART方案调整，方案选择的原则是更换至少2种ART药物，最好选择3种具有抗病毒活性的药物；新的ART方案通常应包括1种具有完全抗病毒活性的增强PI或INSTI或未曾使用过的新的作用机制药物如衣壳抑制剂和FI，或上述药物联合应用（A1）。 推荐意见32 低病毒血症（LLV）需评估患者的依从性、耐受性和药物不良反应、药物相互作用（A1）。LLV通常不需要改变治疗方案（B1），但需每3个月监测1次HIV RNA，以评估是否需要调整ART方案（C1）。 IRIS 推荐意见33 HIV感染者接受ART后出现如发热、潜伏感染变成活动性感染、原有感染的加重或恶化等炎症相关表现时，应考虑存在IRIS的可能，但应注意排除由HIV疾病进展、新发感染、HIV相关肿瘤、药物不良反应、治疗失败等情况带来的干扰。临床上应根据IRIS的严重程度，开始或继续治疗相关机会性感染，严重者可短期应用糖皮质激素或非甾体抗炎药（C1）。 免疫功能重建不全 推荐意见34 接受ART 4年以上，外周血病毒载量低于检测下限（＜50拷贝/mL）超过3年，CD4+T淋巴细胞计数仍持续低于350个/μL，同时排除其他可能导致CD4+T淋巴细胞计数长期低下的原因，需考虑为免疫功能重建不全（B1）。 推荐意见35 免疫功能重建不全缺乏明确有效的治疗方法，临床应定期监测，并需根据CD4+T淋巴细胞水平进行机会性感染的预防和NADE的筛查。对于已实现病毒学抑制的患者，不建议为改善免疫重建而随意进行ART调整（B1）。 AIDS相关肿瘤 推荐意见36 HIV感染者在随访过程中应注意筛查AIDS定义性肿瘤和非AIDS定义性肿瘤。年龄在25岁以上的女性HIV感染者，建议定期进行宫颈癌的筛查（C1）。所有AIDS合并肿瘤的患者均建议尽早启动ART，需注意抗病毒药物和抗肿瘤药物之间的相互作用，应选用骨髓抑制作用和药物相互作用小的ART方案。提倡MDT模式来为HIV合并肿瘤患者提供标准化诊疗（C1）。 HIV母婴传播阻断及单阳家庭生育 抗反转录病毒药物干预 推荐意见37 所有感染HIV的孕妇不论其CD4+T淋巴细胞计数多少或疾病临床分期如何，均应尽早终身接受ART（B1）；孕妇ART首选包含多替拉韦或拉替拉韦的三联ART方案（A1）。 推荐意见38 HIV感染母亲所生婴儿应在出生后尽早（6 h内）预防性服用抗病毒药物，并根据暴露风险来确定服药方案（B1）。 产后喂养指导 推荐意见39 HIV阳性孕产妇所生婴儿推荐科学喂养，避免母乳喂养，杜绝混合喂养（A1）；对因不具备人工喂养条件而选择母乳喂养的感染产妇及其家人，要做好充分的咨询和知情，指导其坚持正确的纯母乳喂养，且在整个哺乳期间必须坚持ART，喂养时间不超过6个月（A1）。 HIV暴露前后预防与阻断 暴露后预防（PEP） 推荐意见40 HIV预防阻断前检测建议进行HIV RNA检测，尤其对既往有阻断用药史的求询者（A1）；在发生HIV暴露后尽可能在最短的时间内（尽可能在2 h内）进行预防性用药，最好在24 h内，但不超过72 h，连续服用28 d（C1）；暴露后阻断方案首选 恩曲他滨/替诺福韦（FTC/TDF）或恩曲他滨/丙酚替诺福韦（FTC/TAF）联合INSTI（比克替拉韦[BIC]或多替拉韦或拉替拉韦）的方案（C1）。 暴露前预防（PrEP） 推荐意见41 实施PrEP前应做好HIV暴露风险评估和医学及适应性评估（C1），PrEP的口服方案有两种，分别为每日服药方案和事件驱动服药方案，药物可选择FTC/TDF（或FTC/TAF）（A1）；不能选择口服药物的可选择长效卡替拉韦（CAB-LA）肌内注射的方案（A1）。 HIV感染的全程管理 推荐意见42 所有HIV感染者均推荐按照全程管理的模式来进行管理（C1）。 推荐意见43 对于晚发现的HIV感染者尤其是处于HIV感染疾病晚期的患者要进行各种机会性感染的筛查，应将结核病和隐球菌病的筛查作为临床诊疗常规（A1）。 推荐意见44 推荐对CD4+T淋巴细胞计数＜200个/μL的HIV感染者开展血清CrAg筛查，阳性者应进行脑脊液检查以排除隐球菌性脑膜炎的可能（B1）。 推荐意见45 启动ART之前，建议进行相应的基线检测和评估，这些检测包括：HIV RNA、CD4+T淋巴细胞计数、HIV耐药检测、血常规、尿常规、肝肾功能、血糖、血脂、是否存在合并感染（如病毒性肝炎、隐球菌病、结核病、STI等）的相关检测等（C1）。 推荐意见46 需特别关注脆弱人群抗病毒治疗和随访的相关问题，脆弱人群主要包括：年龄超过50岁的老年患者；儿童患者；孕妇；具有多种基础疾病的患者；免疫高度抑制的患者如CD4+T淋巴细胞计数＜50个/μL；ART后免疫功能重建不全的患者。这类患者要更为积极地进行ART，积极治疗基础疾病，注意多学科协作诊治（C1）。 推荐意见47 对于ART后病毒得到有效抑制的患者，不建议随意进行治疗方案的调整。优化治疗应当以维持病毒抑制为基础，并且不对未来的药物选择构成威胁。在进行ART方案优化时，应特别注意患者之前是否存在HIV耐药及有无合并HBV或HCV感染的情况（A1）；病毒学抑制且无传播性或获得性HIV耐药史的HIV感染者，通常可以转换为任何首选推荐的初始ART方案并维持病毒学抑制（A1）。 推荐意见48 所有HIV感染者均应定期接受CVD风险评估、筛查和预防干预，对于CVD风险高的患者，应相应调整ART方案，同时积极控制相关CVD风险因素如戒烟、血糖、血脂、肥胖和血压等（C1）。 推荐意见49 应创造各种条件促进HIV/AIDS患者便利接受各种诊疗服务，确保医疗服务的可持续性（B1）；应对HIV/AIDS患者进行疫苗接种指导（C1）。 通信作者 北京协和医院 李太生 感染内科主任，教授，主任医师，博士生导师。中国国家卫生健康委艾滋病专家咨询委员会临床组组长，中华医学会感染性疾病分会副主任委员兼艾滋病学组组长，曾任中华医学会热带病和寄生虫分会主任委员。共发表学术论文200余篇，其中在SCI收录的杂志上发表论文50余篇，被他人引用超过2500次。 推荐阅读 每月一次，效果可维持11个月！《自然-医学》：三联抗体组合长效抑制HIV 80%的中风可预防！权威指南：降压、降糖、地中海饮食……关注10大要点更新 全球约30%的人有脂肪肝！《柳叶刀》子刊：3大危险因素、4类治疗策略 JAMA子刊：结直肠癌肝转移一线治疗，“简化方案”有望成为首选 欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。 参考资料 [1] 中华医学会感染病学分会艾滋病学组, 中国疾病预防控制中心. 中国艾滋病诊疗指南(2024版)[J]. 协和医学杂志, 2024, 15(6): 1261-1288. DOI: 10.12290/xhyxzz.2024-0766 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 《协和医学杂志》倡导尊重和保护知识产权，欢迎转载、引用，但需取得本平台授权。如您对文章内容及版权存疑，请发送邮件至medj@pumch.cn，我们会与您及时沟通处理。图文内容仅供交流、学习使用，不以盈利为目的；科普内容仅用于大众健康知识普及，读者切勿作为个体诊疗根据，自行处置，以免延误治疗。治病就医相关需求请于北京协和医院APP线上或线下就诊。 分享，点赞，在看，传递医学新知

FOSTER CITY, Calif.--( BUSINESS WIRE )--Gilead Sciences, Inc. (Nasdaq: GILD) announced today its third quarter 2024 results of operations. “Gilead’s third quarter results are the strongest of the year to date, with 7% year-over-year revenue growth, including 13% year-over-year growth for Biktarvy. Based on this very strong topline growth and disciplined operating expense management, we are increasing our full year revenue, operating income, and earnings per share guidance,” said Daniel O’Day, Gilead’s Chairman and Chief Executive Officer. “We are excited to further increase our impact for patients and communities in the months ahead. This includes building on the momentum from the U.S. launch of Livdelzi for primary biliary cholangitis and preparing for the potential launch of the first twice-yearly option for HIV prevention option, lenacapavir.” Third Quarter 2024 Financial Results Total third quarter 2024 revenue increased 7% to $7.5 billion compared to the same period in 2023, primarily due to higher sales in HIV as well as in Veklury ® (remdesivir), Oncology and Liver Disease. Diluted earnings per share (“EPS”) was $1.00 in the third quarter 2024 compared to $1.73 in the same period in 2023. The decrease was primarily driven by a pre-tax in-process research and development (“IPR&D”) impairment of $1.75 billion, or $1.04 per share net of tax impact, related to assets acquired by Gilead from Immunomedics, Inc. (“Immunomedics”) in 2020, as well as higher acquired IPR&D expense. This was partially offset by higher product sales and higher net unrealized gains on equity securities. Non-GAAP diluted EPS was $2.02 in the third quarter 2024 compared to $2.29 in the same period in 2023. The decrease was primarily driven by higher acquired IPR&D and tax expense, partially offset by higher product sales. As of September 30, 2024, Gilead had $5.0 billion of cash, cash equivalents and marketable debt securities compared to $8.4 billion as of December 31, 2023. The decrease primarily reflects the $3.9 billion acquisition of CymaBay Therapeutics, Inc. During the third quarter 2024 Gilead generated $4.3 billion in operating cash flow. During the third quarter 2024 Gilead paid dividends of $983 million and repurchased $300 million of common stock. Third Quarter 2024 Product Sales Total third quarter 2024 product sales increased 7% to $7.5 billion compared to the same period in 2023. Total third quarter 2024 product sales, excluding Veklury, increased 7% to $6.8 billion compared to the same period in 2023, primarily due to higher sales in HIV as well as in Oncology and Liver Disease. HIV product sales increased 9% to $5.1 billion in the third quarter 2024 compared to the same period in 2023, driven by higher average realized price, primarily due to shifts in channel mix, and higher demand, partially offset by inventory dynamics. Biktarvy ® (bictegravir 50mg/emtricitabine 200mg (“FTC”)/tenofovir alafenamide 25mg (“TAF”)) sales increased 13% to $3.5 billion in the third quarter 2024 compared to the same period in 2023, primarily driven by higher demand and average realized price, partially offset by inventory dynamics. Descovy ® (FTC 200mg/TAF 25mg) sales increased 15% to $586 million in the third quarter 2024 compared to the same period in 2023, primarily driven by higher demand and average realized price, partially offset by inventory dynamics. The Liver Disease portfolio sales increased 4% to $733 million in the third quarter 2024 compared to the same period in 2023. This was primarily driven by higher demand in viral hepatitis medicines, partially offset by unfavorable pricing dynamics. Veklury sales increased 9% to $692 million in the third quarter 2024 compared to the same period in 2023, primarily driven by increased rates of COVID-19 related hospitalizations, particularly in the United States. Cell Therapy product sales of $485 million in the third quarter 2024 were relatively flat compared to the same period in 2023. Yescarta ® (axicabtagene ciloleucel) sales decreased 1% to $387 million in the third quarter 2024 compared to the same period in 2023, reflecting increased in- and out-of-class competition in the United States, partially offset by increased demand in relapsed or refractory (“R/R”) large B-cell lymphoma (“LBCL”) in other regions. Tecartus ® (brexucabtagene autoleucel) sales increased 2% to $98 million in the third quarter 2024 compared to the same period in 2023, driven by increased demand in adult acute lymphoblastic leukemia (“ALL”). Trodelvy ® (sacituzumab govitecan-hziy) sales increased 17% to $332 million in the third quarter 2024 compared to the same period in 2023, primarily driven by higher demand across all regions. Third Quarter 2024 Product Gross Margin, Operating Expenses and Effective Tax Rate Product gross margin was 79.1% in the third quarter 2024 compared to 77.6% in the same period in 2023. Non-GAAP product gross margin was 86.8% in the third quarter 2024 compared to 85.9% in the same period in 2023. The increases in GAAP and non-GAAP were primarily driven by product mix. Research & development (“R&D”) expenses and non-GAAP R&D expenses were $1.4 billion in the third quarter 2024 compared to $1.5 billion in the same period in 2023. The decreases were primarily driven by the timing of clinical activities, including the wind-down of the magrolimab and obeldesivir COVID programs. Acquired IPR&D expenses were $505 million in the third quarter 2024, primarily driven by a $320 million charge related to the buy-out of global Livdelzi ® (seladelpar) royalties from Janssen Pharmaceutica NV, as well as payments related to ongoing collaborations. IPR&D impairment was $1.75 billion related to the assets acquired from Immunomedics in 2020 with no similar charges in 2023. Selling, general and administrative (“SG&A”) expenses and non-GAAP SG&A expenses were $1.4 billion in the third quarter 2024 compared to $1.3 billion in the same period in 2023. The increases reflect the timing of commercial activities, including the launch of Livdelzi in the United States, and other corporate activities. The effective tax rate (“ETR”) was (31.1)% in the third quarter 2024 compared to 6.3% in the same period in 2023. The decrease in ETR primarily reflects the impact of a legal entity restructuring and the aforementioned Immunomedics IPR&D impairment expense, partially offset by a prior year decrease in tax reserves that did not repeat. Non-GAAP ETR was 17.5% in the third quarter 2024 compared to 7.0% in the same period in 2023, primarily reflecting the impact of the prior year decrease in tax reserves. Guidance and Outlook For the full-year 2024, Gilead expects: (in millions, except per share amounts) November 6, 2024 Guidance Low End High End Comparison to August 8, 2024 Guidance Product sales $ 27,800 $ 28,100 Previously $27,100 to $27,500 Product sales, excluding Veklury $ 26,000 $ 26,300 Previously $25,800 to $26,200 Veklury $ 1,800 $ 1,800 Previously $1,300 Diluted EPS $ 0.05 $ 0.25 Previously $0.00 to $0.30 Non-GAAP diluted EPS $ 4.25 $ 4.45 Previously $3.60 to $3.90 Additional information and a reconciliation between GAAP and non-GAAP financial information for the 2024 guidance is provided in the accompanying tables. The financial guidance is subject to a number of risks and uncertainties. See the Forward-Looking Statements section below. Key Updates Since Our Last Quarterly Release Virology Announced results of PURPOSE 2, the second Phase 3 study of twice-yearly lenacapavir for HIV prevention, with data presented at the HIV Research for Prevention Conference. In the lenacapavir group, 99.9% of participants did not acquire HIV infection, with 2 incident cases among 2,179 participants. Lenacapavir reduced HIV infections by 96% compared to background HIV incidence in cisgender men and gender-diverse people, and additionally demonstrated superiority to daily Truvada ® (FTC 200mg and tenofovir disoproxil fumarate 300mg; 89% relative risk reduction). Lenacapavir was generally well-tolerated and no significant or new safety concerns were identified. Gilead expects to file for U.S. Food and Drug Administration (“FDA”) approval before the end of the year, with global filings to follow. The use of lenacapavir for the prevention of HIV is investigational. Presented HIV treatment data at the Infection Disease Week (“IDWeek”) meeting, including Week 48 data from the Phase 2 study evaluating the investigational oral once-weekly combination regimen of lenacapavir with Merck’s, known as MSD outside of the United States and Canada (“Merck”), islatravir. In addition, Phase 1a data of the investigational once-weekly GS-1720 and 3-year follow up from the Phase 2/3 CAPELLA trial of twice-yearly lenacapavir in people with multi-drug resistant HIV were also highlighted. Signed royalty-free voluntary licensing agreements with six manufacturers to make and sell generic lenacapavir for HIV prevention and for HIV treatment in heavily treatment-experienced adults with multi-drug resistant HIV in 120 high-incidence, resource-limited countries, subject to regulatory approval of lenacapavir in those markets. Presented data at IDWeek from the Phase 3 BIRCH and OAKTREE trials of investigational obeldesivir in non-hospitalized participants at high-risk or standard-risk for severe COVID-19, respectively. Previously, Gilead announced the early termination of the BIRCH trial and top-line results from the OAKTREE trial which found that while the study did not meet its primary endpoint, obeldesivir was found to have a generally well tolerated safety profile. The detailed data presented add to the breadth of safety data on obeldesivir. Donated approximately 5,000 vials of remdesivir to the Rwanda Medical Supply in response to the Marburg Virus Disease (“MVD”) outbreak for emergency use. Remdesivir is not approved for the treatment of MVD anywhere globally, and the safety and efficacy of this use is not known. Oncology Announced abstracts for the American Society of Hematology 2024 Annual Meeting (“ASH”), including preliminary data from the registrational Phase 2 iMMagine-1 trial evaluating the Arcellx, Inc. (“Arcellx”) partnered investigational CAR T anito-cel (anitocabtagene autoleucel) in R/R multiple myeloma, as well as updated results from the Phase 1 trial. Additionally, the first patient has been dosed in the Phase 3 iMMagine-3 trial in 2L+ R/R multiple myeloma. Announced ASH abstracts for long-term follow-up of Yescarta in R/R indolent non-Hodgkin’s lymphoma and Tecartus in R/R mantle cell lymphoma, as well as real world data for Tecartus in B-cell precursor ALL. Presented Trodelvy data at the International Association for the Study of Lung Cancer World Conference on Lung Cancer across first- and second-line advanced or metastatic non-small cell lung cancer, as well as in extensive-stage small cell lung cancer. The use of Trodelvy for lung cancer is investigational. Announced plans to voluntarily withdraw the U.S. accelerated approval of Trodelvy for use in pre-treated adult patients with locally advanced or metastatic urothelial cancer, following the results of the Phase 3 TROPiCS-04 trial announced in May 2024. Received FDA Regenerative Medicine Advanced Therapy Designation for the evaluation of Yescarta as first-line treatment for adult patients with newly diagnosed, high-risk LBCL, an investigational use. Inflammation Received FDA accelerated approval for Livdelzi for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (“UDCA”) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. The use of Livdelzi is not recommended for people who have or develop decompensated cirrhosis. Corporate Announced a strategic collaboration with Genesis Therapeutics, Inc. (“Genesis”) to discover and develop novel small molecule therapies across multiple targets using Genesis’ GEMS AI platform. The Board declared a quarterly dividend of $0.77 per share of common stock for the fourth quarter of 2024. The dividend is payable on December 30, 2024, to stockholders of record at the close of business on December 13, 2024. Future dividends will be subject to Board approval. Certain amounts and percentages in this press release may not sum or recalculate due to rounding. Conference Call At 1:30 p.m. Pacific Time today, Gilead will host a conference call to discuss Gilead’s results. A live webcast will be available on http://investors.gilead.com and will be archived on www.gilead.com for one year. Non-GAAP Financial Information The information presented in this document has been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”), unless otherwise noted as non-GAAP. Management believes non-GAAP information is useful for investors, when considered in conjunction with Gilead’s GAAP financial information, because management uses such information internally for its operating, budgeting and financial planning purposes. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of Gilead’s operating results as reported under GAAP. Non-GAAP financial information generally excludes acquisition-related expenses including amortization of acquired intangible assets and other items that are considered unusual or not representative of underlying trends of Gilead’s business, fair value adjustments of equity securities and discrete and related tax charges or benefits associated with such exclusions as well as changes in tax-related laws and guidelines, transfers of intangible assets between certain legal entities, and legal entity restructurings. Although Gilead consistently excludes the amortization of acquired intangible assets from the non-GAAP financial information, management believes that it is important for investors to understand that such intangible assets were recorded as part of acquisitions and contribute to ongoing revenue generation. Non-GAAP measures may be defined and calculated differently by other companies in the same industry. Reconciliations of the non-GAAP financial measures to the most directly comparable GAAP financial measures are provided in the accompanying tables. About Gilead Sciences 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. Forward-Looking Statements Statements included in this press release that are not historical in nature are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Gilead cautions readers that forward-looking statements are subject to certain risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include those relating to: Gilead’s ability to achieve its anticipated full year 2024 financial results, including as a result of the uncertainty of the amount and timing of Veklury revenues; Gilead’s ability to make progress on any of its long-term ambitions or priorities laid out in its corporate strategy; Gilead’s ability to accelerate or sustain revenues for its virology, oncology and other programs; Gilead’s ability to realize the potential benefits of acquisitions, collaborations or licensing arrangements, including the arrangements with Arcellx, Genesis and Merck; patent protection and estimated loss of exclusivity for our products and product candidates; Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timeframes or at all, the possibility of unfavorable results from ongoing and additional clinical trials, including those involving Trodelvy, anito-cel, GS-1720, lenacapavir, and obeldesivir (such as the BIRCH, CAPELLA, iMMagine-1, iMMagine-3, OAKTREE, and PURPOSE-2 studies), and the risk that safety and efficacy data from clinical trials may not warrant further development of Gilead’s product candidates or the product candidates of Gilead’s strategic partners; Gilead’s ability to submit new drug applications for new product candidates or expanded indications in the currently anticipated timelines, including for lenacapavir for HIV PrEP; Gilead’s ability to receive or maintain regulatory approvals in a timely manner or at all, and the risk that any such approvals, if granted, may be subject to significant limitations on use and may be subject to withdrawal or other adverse actions by the applicable regulatory authority; Gilead’s ability to successfully commercialize its products; the risk of potential disruptions to the manufacturing and supply chain of Gilead’s products; pricing and reimbursement pressures from government agencies and other third parties, including required rebates and other discounts; a larger than anticipated shift in payer mix to more highly discounted payer segments; market share and price erosion caused by the introduction of generic versions of Gilead products; the risk that physicians and patients may not see advantages of Gilead’s products over other therapies and may therefore be reluctant to prescribe the products, including Livdelzi; and other risks identified from time to time in Gilead’s reports filed with the SEC, including annual reports on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K. In addition, Gilead makes estimates and judgments that affect the reported amounts of assets, liabilities, revenues and expenses and related disclosures. Gilead bases its estimates on historical experience and on various other market specific and other relevant assumptions that it believes to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. There may be other factors of which Gilead is not currently aware that may affect matters discussed in the forward-looking statements and may also cause actual results to differ significantly from these estimates. Further, results for the quarter ended September 30, 2024 are not necessarily indicative of operating results for any future periods. Gilead directs readers to its press releases, annual reports on Form 10-K, quarterly reports on Form 10-Q and other subsequent disclosure documents filed with the SEC. Gilead claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. The reader is cautioned that forward-looking statements are not guarantees of future performance 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 to update or supplement any such forward-looking statements other than as required by law. Any forward-looking statements speak only as of the date hereof or as of the dates indicated in the statements. Gilead owns or has rights to various trademarks, copyrights and trade names used in its business, including the following: GILEAD ® , GILEAD SCIENCES ® , KITE TM , AMBISOME ® , ATRIPLA ® , BIKTARVY ® , CAYSTON ® , COMPLERA ® , DESCOVY ® , DESCOVY FOR PREP ® , EMTRIVA ® , EPCLUSA ® , EVIPLERA ® , GENVOYA ® , HARVONI ® , HEPCLUDEX ® , HEPSERA ® , JYSELECA ® , LIVDELZI ® , LETAIRIS ® , ODEFSEY ® , SOVALDI ® , STRIBILD ® , SUNLENCA ® , TECARTUS ® , TRODELVY ® , TRUVADA ® , TRUVADA FOR PREP ® , TYBOST ® , VEKLURY ® , VEMLIDY ® , VIREAD ® , VOSEVI ® , YESCARTA ® and ZYDELIG ® . For more information on Gilead Sciences, Inc., please visit www.gilead.com or call the Gilead Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235). GILEAD SCIENCES, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited) Three Months Ended Nine Months Ended September 30, September 30, (in millions, except per share amounts) 2024 2023 2024 2023 Revenues: Product sales $ 7,515 $ 6,994 $ 21,074 $ 19,864 Royalty, contract and other revenues 30 56 111 138 Total revenues 7,545 7,051 21,185 20,002 Costs and expenses: Cost of goods sold 1,574 1,565 4,670 4,408 Research and development expenses 1,395 1,457 4,266 4,310 Acquired in-process research and development expenses 505 91 4,674 808 In-process research and development impairment 1,750 — 4,180 — Selling, general and administrative expenses 1,433 1,315 4,184 4,482 Total costs and expenses 6,657 4,428 21,975 14,009 Operating income (loss) 888 2,623 (790 ) 5,993 Interest expense 238 232 728 692 Other (income) expense, net (306 ) 72 (41 ) 95 Income (loss) before income taxes 956 2,318 (1,477 ) 5,206 Income tax (benefit) expense (297 ) 146 (174 ) 1,010 Net income (loss) 1,253 2,172 (1,303 ) 4,196 Net loss attributable to noncontrolling interest — (8 ) — (40 ) Net income (loss) attributable to Gilead $ 1,253 $ 2,180 $ (1,303 ) $ 4,236 Basic earnings (loss) per share attributable to Gilead $ 1.00 $ 1.75 $ (1.04 ) $ 3.39 Shares used in basic earnings (loss) per share attributable to Gilead calculation 1,247 1,248 1,247 1,249 Diluted earnings (loss) per share attributable to Gilead $ 1.00 $ 1.73 $ (1.04 ) $ 3.37 Shares used in diluted earnings (loss) per share attributable to Gilead calculation 1,254 1,257 1,247 1,259 Supplemental Information: Cash dividends declared per share $ 0.77 $ 0.75 $ 2.31 $ 2.25 Product gross margin 79.1 % 77.6 % 77.8 % 77.8 % Research and development expenses as a % of revenues 18.5 % 20.7 % 20.1 % 21.5 % Selling, general and administrative expenses as a % of revenues 19.0 % 18.6 % 19.8 % 22.4 % Operating margin 11.8 % 37.2 % (3.7 )% 30.0 % Effective tax rate (31.1 )% 6.3 % 11.8 % 19.4 % GILEAD SCIENCES, INC. TOTAL REVENUE SUMMARY (unaudited) Three Months Ended Nine Months Ended September 30, September 30, (in millions, except percentages) 2024 2023 Change 2024 2023 Change Product sales: HIV $ 5,073 $ 4,667 9% $ 14,160 $ 13,482 5% Liver Disease 733 706 4% 2,302 2,093 10% Oncology 816 769 6% 2,446 2,167 13% Other 201 216 (7)% 705 658 7% Total product sales excluding Veklury 6,823 6,358 7% 19,613 18,400 7% Veklury 692 636 9% 1,461 1,465 —% Total product sales 7,515 6,994 7% 21,074 19,864 6% Royalty, contract and other revenues 30 56 (46)% 111 138 (19)% Total revenues $ 7,545 $ 7,051 7% $ 21,185 $ 20,002 6% GILEAD SCIENCES, INC. NON-GAAP FINANCIAL INFORMATION (1) (unaudited) Three Months Ended Nine Months Ended September 30, September 30, (in millions, except percentages) 2024 2023 Change 2024 2023 Change Non-GAAP: Cost of goods sold $ 995 $ 985 1% $ 2,933 $ 2,717 8% Research and development expenses $ 1,382 $ 1,453 (5)% $ 4,120 $ 4,268 (3)% Acquired IPR&D expenses (2) $ 505 $ 91 NM $ 4,674 $ 808 NM Selling, general and administrative expenses $ 1,405 $ 1,298 8% $ 4,051 $ 4,464 (9)% Other (income) expense, net $ (48 ) $ (96 ) (50)% $ (189 ) $ (261 ) (28)% Diluted earnings per share attributable to Gilead $ 2.02 $ 2.29 (12)% $ 2.72 $ 5.00 (46)% Shares used in non-GAAP diluted earnings per share attributable to Gilead calculation 1,254 1,257 —% 1,254 1,259 —% Product gross margin 86.8 % 85.9 % 84 bps 86.1 % 86.3 % -24 bps Research and development expenses as a % of revenues 18.3 % 20.6 % -229 bps 19.4 % 21.3 % -189 bps Selling, general and administrative expenses as a % of revenues 18.6 % 18.4 % 21 bps 19.1 % 22.3 % -320 bps Operating margin 43.2 % 45.7 % -255 bps 25.5 % 38.7 % -1320 bps Effective tax rate 17.5 % 7.0 % 1052 bps 30.0 % 14.5 % 1552 bps ________________________________ NM - Not Meaningful (1) Refer to Non-GAAP Financial Information section above for further disclosures on non-GAAP financial measures. A reconciliation between GAAP and non-GAAP financial information is provided in the tables below. (2) Equal to GAAP financial information. GILEAD SCIENCES, INC. RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL INFORMATION (unaudited) Three Months Ended Nine Months Ended September 30, September 30, (in millions, except percentages and per share amounts) 2024 2023 2024 2023 Cost of goods sold reconciliation: GAAP cost of goods sold $ 1,574 $ 1,565 $ 4,670 $ 4,408 Acquisition-related – amortization (1) (579 ) (581 ) (1,737 ) (1,691 ) Restructuring — — 1 — Non-GAAP cost of goods sold $ 995 $ 985 $ 2,933 $ 2,717 Product gross margin reconciliation: GAAP product gross margin 79.1 % 77.6 % 77.8 % 77.8 % Acquisition-related – amortization (1) 7.7 % 8.3 % 8.2 % 8.5 % Restructuring — % — % (— )% — % Non-GAAP product gross margin 86.8 % 85.9 % 86.1 % 86.3 % Research and development expenses reconciliation: GAAP research and development expenses $ 1,395 $ 1,457 $ 4,266 $ 4,310 Acquisition-related – other costs (2) (9 ) 1 (78 ) (37 ) Restructuring (5 ) (5 ) (68 ) (5 ) Non-GAAP research and development expenses $ 1,382 $ 1,453 $ 4,120 $ 4,268 IPR&D impairment reconciliation: GAAP IPR&D impairment $ 1,750 $ — $ 4,180 $ — IPR&D impairment (1,750 ) — (4,180 ) — Non-GAAP IPR&D impairment $ — $ — $ — $ — Selling, general and administrative expenses reconciliation: GAAP selling, general and administrative expenses $ 1,433 $ 1,315 $ 4,184 $ 4,482 Acquisition-related – other costs (2) (5 ) — (88 ) (2 ) Restructuring (23 ) (17 ) (45 ) (17 ) Non-GAAP selling, general and administrative expenses $ 1,405 $ 1,298 $ 4,051 $ 4,464 Operating income (loss) reconciliation: GAAP operating income (loss) $ 888 $ 2,623 $ (790 ) $ 5,993 Acquisition-related – amortization (1) 579 581 1,737 1,691 Acquisition-related – other costs (2) 13 (1 ) 167 39 Restructuring 28 22 112 22 IPR&D impairment 1,750 — 4,180 — Non-GAAP operating income $ 3,258 $ 3,224 $ 5,406 $ 7,745 Operating margin reconciliation: GAAP operating margin 11.8 % 37.2 % (3.7 )% 30.0 % Acquisition-related – amortization (1) 7.7 % 8.2 % 8.2 % 8.5 % Acquisition-related – other costs (2) 0.2 % — % 0.8 % 0.2 % Restructuring 0.4 % 0.3 % 0.5 % 0.1 % IPR&D impairment 23.2 % — % 19.7 % — % Non-GAAP operating margin 43.2 % 45.7 % 25.5 % 38.7 % Other (income) expense, net reconciliation: GAAP other (income) expense, net $ (306 ) $ 72 $ (41 ) $ 95 Gain (loss) from equity securities, net 258 (168 ) (148 ) (356 ) Non-GAAP other (income) expense, net $ (48 ) $ (96 ) $ (189 ) $ (261 ) Income (loss) before income taxes reconciliation: GAAP income (loss) before income taxes $ 956 $ 2,318 $ (1,477 ) $ 5,206 Acquisition-related – amortization (1) 579 581 1,737 1,691 Acquisition-related – other costs (2) 13 (1 ) 167 39 Restructuring 28 22 112 22 IPR&D impairment 1,750 — 4,180 — (Gain) loss from equity securities, net (258 ) 168 148 356 Non-GAAP income before income taxes $ 3,068 $ 3,088 $ 4,866 $ 7,314 GILEAD SCIENCES, INC. RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL INFORMATION - (Continued) (unaudited) Three Months Ended Nine Months Ended September 30, September 30, (in millions, except percentages and per share amounts) 2024 2023 2024 2023 Income tax (benefit) expense reconciliation: GAAP income tax (benefit) expense $ (297 ) $ 146 $ (174 ) $ 1,010 Income tax effect of non-GAAP adjustments: Acquisition-related – amortization (1) 121 120 363 347 Acquisition-related – other costs (2) 2 — 39 8 Restructuring 4 5 21 5 IPR&D impairment 440 — 1,051 — (Gain) loss from equity securities, net (46 ) 4 (52 ) 5 Discrete and related tax charges (3) 314 (58 ) 214 (314 ) Non-GAAP income tax expense $ 538 $ 216 $ 1,461 $ 1,061 Effective tax rate reconciliation: GAAP effective tax rate (31.1 )% 6.3 % 11.8 % 19.4 % Income tax effect of above non-GAAP adjustments and discrete and related tax adjustments (3) 48.6 % 0.7 % 18.2 % (4.9 )% Non-GAAP effective tax rate 17.5 % 7.0 % 30.0 % 14.5 % Net income (loss) attributable to Gilead reconciliation: GAAP net income (loss) attributable to Gilead $ 1,253 $ 2,180 $ (1,303 ) $ 4,236 Acquisition-related – amortization (1) 458 461 1,374 1,345 Acquisition-related – other costs (2) 11 (1 ) 128 31 Restructuring 24 17 92 17 IPR&D impairment 1,310 — 3,129 — (Gain) loss from equity securities, net (212 ) 164 200 351 Discrete and related tax charges (3) (314 ) 58 (214 ) 314 Non-GAAP net income attributable to Gilead $ 2,531 $ 2,879 $ 3,405 $ 6,293 Diluted earnings (loss) per share reconciliation: GAAP diluted earnings (loss) per share $ 1.00 $ 1.73 $ (1.04 ) $ 3.37 Acquisition-related – amortization (1) 0.37 0.37 1.10 1.07 Acquisition-related – other costs (2) 0.01 — 0.10 0.02 Restructuring 0.02 0.01 0.07 0.01 IPR&D impairment 1.04 — 2.51 — (Gain) loss from equity securities, net (0.17 ) 0.13 0.16 0.28 Discrete and related tax charges (3) (0.25 ) 0.05 (0.17 ) 0.25 Difference in shares used for GAAP vs. Non-GAAP — — (0.01 ) — Non-GAAP diluted earnings per share $ 2.02 $ 2.29 $ 2.72 $ 5.00 Non-GAAP adjustment summary: Cost of goods sold adjustments $ 579 $ 581 $ 1,736 $ 1,691 Research and development expenses adjustments 13 4 146 42 IPR&D impairment adjustments 1,750 — 4,180 — Selling, general and administrative expenses adjustments 28 17 133 19 Total non-GAAP adjustments to costs and expenses 2,370 602 6,196 1,752 Other (income) expense, net adjustments (258 ) 168 148 356 Total non-GAAP adjustments before income taxes 2,113 770 6,343 2,108 Income tax effect of non-GAAP adjustments above (521 ) (129 ) (1,421 ) (364 ) Discrete and related tax charges (3) (314 ) 58 (214 ) 314 Total non-GAAP adjustments to net income attributable to Gilead $ 1,278 $ 699 $ 4,708 $ 2,057 ________________________________ (1) Relates to amortization of acquired intangibles. (2) Adjustments include integration expenses, contingent consideration fair value adjustments and other expenses associated with Gilead’s acquisitions of MYR GmbH, MiroBio, Ltd., Tmunity Therapeutics, Inc., XinThera, Inc. and CymaBay Therapeutics, Inc. (3) Represents discrete and related deferred tax charges or benefits primarily associated with acquired intangible assets and in-process research and development, transfers of intangible assets from a foreign subsidiary to Ireland and the United States, and legal entity restructurings. GILEAD SCIENCES, INC. RECONCILIATION OF GAAP TO NON-GAAP 2024 FULL-YEAR GUIDANCE (1) (unaudited) (in millions, except percentages and per share amounts) Provided February 6, 2024 Updated April 25, 2024 Updated August 8, 2024 Updated November 6, 2024 Projected product gross margin GAAP to non-GAAP reconciliation: GAAP projected product gross margin 76.0% - 77.0% 76.0% - 77.0% 76.0% - 77.0% 78.0% Acquisition-related expenses and restructuring expenses ~ 9.0% ~ 9.0% ~ 9.0% ~ 8.0% Non-GAAP projected product gross margin 85.0% - 86.0% 85.0% - 86.0% 85.0% - 86.0% 86.0% Projected operating income GAAP to non-GAAP reconciliation: GAAP projected operating income $8,700 - $9,200 $1,900 - $2,400 $2,100 - $2,500 $1,100 - $1,400 IPR&D impairment, acquisition-related and restructuring expenses ~ 2,500 ~ 5,100 ~ 5,100 ~ 6,900 Non-GAAP projected operating income $11,200 - $11,700 $7,000 - $7,500 $7,200 - $7,600 $8,000 - $8,300 Projected effective tax rate GAAP to non-GAAP reconciliation: GAAP projected effective tax rate ~ 21% ~ 65% ~ 87% ~ 56% Income tax effect of above non-GAAP adjustments and fair value adjustments of equity securities, and discrete and related tax adjustments (~ 2%) (~ 35%) (~ 57%) (~ 29%) Non-GAAP projected effective tax rate ~ 19% ~ 30% ~ 30% ~ 27% Projected diluted EPS GAAP to non-GAAP reconciliation: GAAP projected diluted EPS $5.15 - $5.55 $0.10 - $0.50 $0.00 - $0.30 $0.05 - $0.25 IPR&D impairment, acquisition-related and restructuring expenses, fair value adjustments of equity securities and discrete and related tax adjustments ~ 1.70 ~ 3.35 ~ 3.60 ~ 4.20 Non-GAAP projected diluted EPS $6.85 - $7.25 $3.45 - $3.85 $3.60 - $3.90 $4.25 - $4.45 ________________________________ (1) Our full-year guidance excludes the potential impact of any (i) acquisitions or business development transactions that have not been executed, (ii) future fair value adjustments of equity securities and (iii) discrete tax charges or benefits associated with changes in tax related laws and guidelines that have not been enacted, as Gilead is unable to project such amounts. The non-GAAP full-year guidance includes non-GAAP adjustments to actual current period results as well as adjustments for the known future impact associated with events that have already occurred, such as future amortization of our intangible assets and the future impact of discrete and related deferred tax charges or benefits primarily associated with acquired intangible assets and in-process research and development, transfers of intangible assets from a foreign subsidiary to Ireland and the United States, and legal entity restructurings. GILEAD SCIENCES, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited) September 30, December 31, (in millions) 2024 2023 Assets Cash, cash equivalents and marketable debt securities $ 5,037 $ 8,428 Accounts receivable, net 4,587 4,660 Inventories 3,435 3,366 Property, plant and equipment, net 5,391 5,317 Intangible assets, net 20,546 26,454 Goodwill 8,314 8,314 Other assets 7,215 5,586 Total assets $ 54,525 $ 62,125 Liabilities and Stockholders’ Equity Current liabilities $ 11,725 $ 11,280 Long-term liabilities 24,409 28,096 Stockholders’ equity (1) 18,390 22,749 Total liabilities and stockholders’ equity $ 54,525 $ 62,125 ________________________________ (1) As of September 30, 2024 and December 31, 2023, there were 1,246 shares of common stock issued and outstanding. GILEAD SCIENCES, INC. SELECTED CASH FLOW INFORMATION (unaudited) Three Months Ended Nine Months Ended September 30, September 30, (in millions) 2024 2023 2024 2023 Net cash provided by operating activities $ 4,309 $ 1,756 $ 7,853 $ 5,837 Net cash used in investing activities (710 ) (229 ) (3,224 ) (1,538 ) Net cash used in financing activities (1,379 ) (1,518 ) (5,693 ) (4,026 ) Effect of exchange rate changes on cash and cash equivalents 44 (7 ) 15 20 Net change in cash and cash equivalents 2,265 1 (1,049 ) 293 Cash and cash equivalents at beginning of period 2,772 5,704 6,085 5,412 Cash and cash equivalents at end of period $ 5,037 $ 5,705 $ 5,037 $ 5,705 Three Months Ended Nine Months Ended September 30, September 30, (in millions) 2024 2023 2024 2023 Net cash provided by operating activities $ 4,309 $ 1,756 $ 7,853 $ 5,837 Capital expenditures (140 ) (122 ) (376 ) (370 ) Free cash flow (1) $ 4,169 $ 1,633 $ 7,478 $ 5,467 ________________________________ (1) Free cash flow is a non-GAAP liquidity measure. Please refer to our disclosures in the Non-GAAP Financial Information section above. GILEAD SCIENCES, INC. PRODUCT SALES SUMMARY (unaudited) Three Months Ended Nine Months Ended September 30, September 30, (in millions) 2024 2023 2024 2023 HIV Biktarvy – U.S. $ 2,826 $ 2,504 $ 7,726 $ 7,104 Biktarvy – Europe 375 313 1,110 920 Biktarvy – Rest of World 272 268 814 717 3,472 3,085 9,649 8,741 Descovy – U.S. 534 460 1,339 1,314 Descovy – Europe 24 25 75 75 Descovy – Rest of World 28 26 82 86 586 511 1,496 1,475 Genvoya – U.S. 384 433 1,088 1,305 Genvoya – Europe 44 47 138 157 Genvoya – Rest of World 21 23 66 81 449 503 1,292 1,544 Odefsey – U.S. 248 257 705 754 Odefsey – Europe 69 74 217 223 Odefsey – Rest of World 9 11 30 33 326 343 952 1,011 Symtuza - Revenue share (1) – U.S. 103 96 338 278 Symtuza - Revenue share (1) – Europe 33 32 101 101 Symtuza - Revenue share (1) – Rest of World 3 3 9 10 139 131 448 390 Other HIV (2) – U.S. 65 56 190 192 Other HIV (2) – Europe 26 28 96 91 Other HIV (2) – Rest of World 9 9 36 38 100 94 322 321 Total HIV – U.S. 4,161 3,807 11,386 10,949 Total HIV – Europe 570 519 1,737 1,568 Total HIV – Rest of World 342 341 1,038 965 5,073 4,667 14,160 13,482 Liver Disease Sofosbuvir / Velpatasvir (3) – U.S. 222 215 737 643 Sofosbuvir / Velpatasvir (3) – Europe 67 76 230 250 Sofosbuvir / Velpatasvir (3) – Rest of World 96 85 299 266 385 377 1,266 1,159 Vemlidy – U.S. 126 112 338 295 Vemlidy – Europe 11 9 33 28 Vemlidy – Rest of World 95 106 328 322 232 228 699 645 Other Liver Disease (4) – U.S. 45 49 134 113 Other Liver Disease (4) – Europe 54 33 148 112 Other Liver Disease (4) – Rest of World 17 20 55 64 116 102 337 289 Total Liver Disease – U.S. 393 376 1,210 1,051 Total Liver Disease – Europe 132 119 411 390 Total Liver Disease – Rest of World 207 211 682 652 733 706 2,302 2,093 Veklury Veklury – U.S. 393 258 784 607 Veklury – Europe 81 65 204 227 Veklury – Rest of World 219 313 473 630 692 636 1,461 1,465 GILEAD SCIENCES, INC. PRODUCT SALES SUMMARY - (Continued) (unaudited) Three Months Ended Nine Months Ended September 30, September 30, (in millions) 2024 2023 2024 2023 Oncology Cell Therapy Tecartus – U.S. 63 64 181 179 Tecartus – Europe 29 27 102 83 Tecartus – Rest of World 6 4 22 11 98 96 305 272 Yescarta – U.S. 145 197 502 624 Yescarta – Europe 182 154 509 408 Yescarta – Rest of World 60 40 170 99 387 391 1,181 1,130 Total Cell Therapy – U.S. 208 261 683 802 Total Cell Therapy – Europe 211 181 611 491 Total Cell Therapy – Rest of World 66 45 192 109 485 486 1,485 1,402 Trodelvy Trodelvy – U.S. 226 201 655 551 Trodelvy – Europe 80 62 217 169 Trodelvy – Rest of World 26 21 88 44 332 283 960 764 Total Oncology – U.S. 433 462 1,338 1,354 Total Oncology – Europe 291 243 828 660 Total Oncology – Rest of World 92 65 280 153 816 769 2,446 2,167 Other AmBisome – U.S. 6 12 37 39 AmBisome – Europe 71 63 210 192 AmBisome – Rest of World 52 39 176 150 130 115 424 381 Other (5) – U.S. 47 69 203 197 Other (5) – Europe 8 9 26 31 Other (5) – Rest of World 16 23 52 49 71 101 281 277 Total Other – U.S. 53 82 241 236 Total Other – Europe 80 72 236 224 Total Other – Rest of World 68 62 228 199 201 216 705 658 Total product sales – U.S. 5,433 4,985 14,958 14,196 Total product sales – Europe 1,154 1,017 3,416 3,069 Total product sales – Rest of World 928 992 2,700 2,599 $ 7,515 $ 6,994 $ 21,074 $ 19,864 ________________________________ (1) Represents Gilead’s revenue from cobicistat (“C”), FTC and TAF in Symtuza (darunavir/C/FTC/TAF), a fixed dose combination product commercialized by Janssen Sciences Ireland Unlimited Company. (2) Includes Atripla, Complera/Eviplera, Emtriva, Sunlenca, Stribild, Truvada and Tybost. (3) Includes Epclusa and the authorized generic version of Epclusa sold by Gilead’s separate subsidiary, Asegua Therapeutics LLC (“Asegua”). (4) Includes ledipasvir/sofosbuvir (Harvoni and the authorized generic version of Harvoni sold by Asegua), Hepcludex, Hepsera, Livdelzi, Sovaldi, Viread and Vosevi. (5) Includes Cayston, Jyseleca, Letairis, Ranexa and Zydelig.