Bictegravir

编者按：随着抗逆转录病毒药物的广泛应用，艾滋病已从一种致命性疾病逐步转变为可长期管理的慢性疾病。然而，艾滋病病毒（HIV）感染者仍面临诸多未被满足的临床需求，尤其是对已产生耐药性或难以长期坚持复杂治疗方案的患者而言，治疗选择仍有进一步优化空间。为应对这些挑战，全球范围内已有上百个创新药研发项目持续推进，旨在不断拓展HIV感染治疗的临床边界与更多可能性。作为全球医药创新的赋能者，药明康德始终致力于提供一体化、端到端的新药研发与生产服务，助力全球合作伙伴加速包括HIV感染在内的各类感染性疾病创新疗法的研发进程，惠及更多患者。本周，第33届逆转录病毒与机会性感染会议（CROI）在美国科罗拉多州丹佛市召开，多项HIV在研疗法的最新研究进展相继公布。本文将对相关研究进行盘点，梳理HIV领域的最新动态与发展趋势。 药物：Doravirine/islatravir 开发公司：默沙东（MSD） 进展：三项关键3期试验达主要终点 默沙东公布了三项关键3期临床试验结果，这些研究评估旗下每日一次口服双药单片复方方案doravirine/islatravir（DOR/ISL；100 mg/0.25 mg）在HIV-1成人患者中的疗效与安全性。Doravirine是由默沙东开发的一种每日一次的口服创新非核苷逆转录酶抑制剂。它通过与HIV-1的逆转录酶结合，防止病毒将RNA逆转录为DNA，从而阻断HIV-1病毒复制。它已在美国获批用于治疗未接受过抗病毒疗法的成年HIV-1感染患者。Islatravir则是默沙东研发的一种核苷类逆转录酶易位抑制剂（NRTTI）。 3期双盲临床试验MK-8591A-053在初治的HIV-1成人患者中，评估DOR/ISL与bictegravir/emtricitabine/tenofovir alafenamide（BIC/FTC/TAF；50 mg/200 mg/25 mg）三联疗法相较的疗效与安全性。结果显示，研究达到主要疗效终点，即实现病毒学抑制（HIV-1 RNA＜50拷贝/毫升）的受试者比例。在第48周时，DOR/ISL相较BIC/FTC/TAF达到非劣效性，病毒抑制率分别为91.8%和90.6%（治疗差异1.2%，95% CI：-3.7，6.2，p＜0.001）。两组治疗的安全性特征相似，并与既往研究观察结果一致。药物相关不良事件（AEs）及因药物相关不良事件导致的停药比例在两组间相近（DOR/ISL为14%，BIC/FTC/TAF为18%；因药物相关AEs停药比例分别为1.1%和2.2%）。 此外，研究人员还公布了3期MK-8591A-052与MK-8591A-051试验的最新96周数据。这两项研究评估了在病毒学抑制的HIV-1患者中，由原治疗方案转换至DOR/ISL治疗后，与BIC/FTC/TAF或基线抗逆转录病毒治疗（bART）相较的疗效与安全性。两项研究均显示，DOR/ISL在第96周维持了较高水平的病毒抑制率，其安全性特征与BIC/FTC/TAF及bART相似。这些研究的48周数据支持美国FDA此前所受理DOR/ISL用于HIV-1感染成人患者的新药申请（NDA），拟用于将目前在抗病毒方案下已获得稳定病毒学抑制的成人患者转换至DOR/ISL方案治疗。FDA已将目标审评完成日期设定为2026年4月28日。 药物：Bictegravir/lenacapavir 开发公司：吉利德科学（Gilead Sciences） 进展：两项3期试验数据公布 吉利德科学公布了3期ARTISTRY-1与ARTISTRY-2临床试验的最新数据。结果显示，将病毒学抑制的HIV感染者转换至旗下在研单片复方方案bictegravir/lenacapavir（BIC/LEN；75 mg/50 mg）治疗具有良好的疗效与安全性。 ARTISTRY-1研究结果表明，在既往接受复杂多片治疗方案并实现病毒学抑制的患者中，转换至BIC/LEN单片方案在第48周维持病毒抑制方面达到非劣效性。结果显示，BIC/LEN组中HIV-1 RNA≥50拷贝/毫升的比例为0.8%，对照组为1.1%。两组患者的CD4细胞计数均保持稳定，且未出现治疗过程中产生的耐药性。此外，转换至BIC/LEN治疗与空腹血脂指标改善相关，总胆固醇中位变化为-15 mg/dL，而继续原复杂方案治疗的患者为+2 mg/dL。 ARTISTRY-2研究则显示，在第48周时，BIC/LEN组与HIV获批疗法Biktarvy（bictegravir/emtricitabine/tenofovir alafenamide，B/F/TAF；50 mg/200 mg/25 mg）组维持病毒学抑制的比例相近，分别有1.3%与1.0%的患者出现HIV-1 RNA≥50拷贝/毫升。两组CD4细胞计数及体重指数均保持稳定。耐药性分析显示，大多数病例未检测到治疗相关耐药，仅在BIC/LEN组一名患者中发现孤立的整合酶位点替代，但未表现出表型耐药，也未检测到衣壳突变。安全性方面，两组药物相关不良事件发生率相似，分别为10.4%与12.0%。 药物：VH184、VH499 开发公司：ViiV Healthcare 进展：公布1期临床研究结果 ViiV Healthcare公布其第三代整合酶链转移抑制剂（INSTI）长效制剂VH184的1期临床研究数据。结果显示，单次注射即可维持药物体内浓度长达6个月，展现出每年两次给药的潜力。体外研究进一步表明，VH184在耐药HIV株中较bictegravir具有更强活性和更优化的耐药性特征。安全性方面，该药总体耐受性良好，不良反应主要为轻度1级注射部位反应，如红斑、疼痛和结节，较少出现2级或3级反应，其安全性特征与既往研究及已获批INSTI药物相似。 与此同时，ViiV Healthcare还公布了在研衣壳抑制剂VH499的1期研究数据，该药同样显示出实现超长效（ULA）半年一次给药的潜力。在正在进行的研究中，未感染HIV的成人受试者接受100 mg至1200 mg剂量范围内的单次肌内或皮下注射，结果显示两种给药方式均可在较长时间内维持稳定药物浓度。VH499整体耐受性良好，最常见的不良反应为注射部位反应，主要表现为1级或2级注射部位疼痛，多为轻至中度且持续时间较短。研究期间未报告严重不良事件，也未出现因不良事件导致的退出病例。研究人员表示，后续研究将基于当前数据进一步优化VH499的给药方案。 药物：Lotivibart、cabotegravir 开发公司：ViiV Healthcare 进展：公布2b期临床研究结果 ViiV Healthcare公布其2b期EMBRACE研究的12个月期中疗效与耐受性数据。该研究评估了在接受稳定抗HIV治疗的成人患者中，每4个月给药一次的广谱中和抗体lotivibart（N6LS）联合每月一次肌内注射长效cabotegravir（CABLA）方案的治疗效果。结果显示，该联合方案在维持病毒学抑制方面表现良好，其中接受静脉注射（IV）lotivibart的患者中有94%维持病毒抑制，皮下注射（SC）组为82%，而标准治疗组为88%。 在12个月期中分析中，联合治疗方案在大多数受试者中持续维持病毒学抑制，仅少数患者出现确证的病毒学失败：IV组为4%（2/50），SC组为6%（3/49），而每日口服标准治疗组为4%（1/26）。安全性方面，lotivibart总体耐受性良好，受试者对治疗的接受度较高。研究期间，关于注射部位反应困扰程度、身体影响、睡眠影响及整体可接受性的平均评分始终维持在“非常可接受”至“完全可接受”范围内。与药物相关的不良事件在IV组发生率较低（24%），低于SC组（53%）。此外，3至4级输注部位反应仅在SC组中报告（16%），IV组未出现此类事件，进一步支持该方案的可耐受性特征。 图片来源：123RF 从本届CROI大会公布的多项研究可以看出，HIV治疗领域正持续向更长效、更简化的治疗模式演进。无论是双药口服方案还是长效注射药物与广谱中和抗体联合策略，研发重点均聚焦于在维持稳定病毒学控制的同时，进一步降低患者治疗负担并改善长期依从性。这些创新方向不仅体现了通过机制优化与给药方式革新推动治疗升级的趋势，也标志着HIV治疗正从“有效控制”迈向“长期高质量管理”的新阶段。 当前，全球仍有百余项HIV在研管线处于临床阶段，涵盖小分子、抗体、疫苗、核酸药物、多肽及细胞治疗等多种技术类型。在这一不断演进的创新生态中，研发模式本身也在发生转变。随着药物复杂度持续提升，从早期研究到商业化生产各阶段的高效协同，正日益成为推动创新成果落地的关键基础。 长期以来，药明康德都在支持全球合作伙伴从药物研究（R）、开发（D）到商业化生产（M）各个阶段的需求，通过独特的一体化、端到端CRDMO模式，助力突破性疗法加速研发进程。 例如，药明康德的传染病平台能够为抗病毒药物和疫苗从早期研究到临床试验的全流程开发提供全面支持。平台覆盖包括HIV在内的20多种病毒的抗病毒药物和疫苗发现，并且对130多种细菌和真菌的抗菌疗法开发同样提供了广泛的支持。 在全球科研与产业协作不断深化的背景下，HIV治疗模式正加速向以患者为中心、兼顾疗效稳定性与长期治疗体验优化的方向演进。随着创新生态不断成熟，推动更多创新疗法更快惠及患者，仍将是产业各方共同努力的目标。 参考资料： [1] Merck Announces Late-Breaking Data from Three Phase 3 Trials Evaluating Doravirine/Islatravir (DOR/ISL), an Investigational, Once-Daily, Two-Drug Regimen for the Treatment of Adults Living with HIV-1 at CROI 2026. Retrieved February 25, 2026 from https://www.merck.com/news/merck-announces-late-breaking-data-from-three-phase-3-trials-evaluating-doravirine-islatravir-dor-isl-an-investigational-once-daily-two-drug-regimen-for-the-treatment-of-adults-living-with-hiv-1/ [2] Gilead’s Single-Tablet Regimen of Bictegravir and Lenacapavir Maintained Virological Suppression in People With HIV Who Switched Antiretroviral Therapy. Retrieved February 25, 2026 from https://www.businesswire.com/news/home/20260224254904/en/Gileads-Single-Tablet-Regimen-of-Bictegravir-and-Lenacapavir-Maintained-Virological-Suppression-in-People-With-HIV-Who-Switched-Antiretroviral-Therapy [3] ViiV Healthcare presents pipeline data for two investigational HIV treatment therapies with potential for twice-yearly dosing. Retrieved February 25, 2026 from https://www.businesswire.com/news/home/20260225546292/en/ViiV-Healthcare-presents-pipeline-data-for-two-investigational-HIV-treatment-therapies-with-potential-for-twice-yearly-dosing [4] ViiV Healthcare reports positive 12-month data showing investigational bNAb lotivibart (N6LS) maintains high levels of viral suppression in long-acting HIV treatment regimen. Retrieved February 25, 2026 from https://www.businesswire.com/news/home/20260225354805/en/ViiV-Healthcare-reports-positive-12-month-data-showing-investigational-bNAb-lotivibart-N6LS-maintains-high-levels-of-viral-suppression-in-long-acting-HIV-treatment-regimen 免责声明：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。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

ViiV is highly mission-driven in our unrelenting commitment to being a trusted partner for all people living with and affected by HIV. Credit: GSK GSK-backed ViiV Healthcare’s VH184 and VH499 show potential for twice-yearly HIV injections, offering long-acting, therapy with improved resistance Recent developments in HIV treatment highlight promising advances in long-acting antiretroviral therapy. ViiV Healthcare, the global specialist HIV company majority owned by GSK with Pfizer and Shionogi as shareholders, has reported encouraging early data for two investigational agents, VH184 and VH499. These therapies aim to reduce the frequency of dosing from daily regimens to potentially twice-yearly injections. The findings suggest both improved potency and tolerability, representing a significant step toward more convenient HIV management. HIV is not a solved problem A third-generation integrase inhibitor VH184, the first third-generation integrase strand transfer inhibitor (INSTI) in development, demonstrated potential for twice-yearly dosing in a phase 1 study of adults without HIV . Administered as a single subcutaneous or intramuscular injection, both formulations maintained drug levels for extended periods, with one sustaining steady concentrations through seven months. Early tolerability data show mostly mild injection site reactions, consistent with approved INSTIs, suggesting VH184 could offer a safe, long-acting alternative to daily therapies. In vitro studies further support VH184’s potential clinical advantages. Compared with bictegravir, VH184 retained activity against a broad spectrum of resistant HIV strains, including viruses with multiple INSTI-associated mutations. This enhanced resistance profile indicates a higher barrier to resistance, a critical consideration for long-term HIV management. ViiV Healthcare is a global specialty HIV company, the only one that is 100% focused on researching and delivering new medicines for people living with, and at risk of, HIV. Credit: GSK Together with its pharmacokinetic profile, these findings position VH184 as a promising candidate for ultra long-acting HIV therapy. An investigational capsid inhibitor VH499, an investigational capsid inhibitor, also showed potential for twice-yearly dosing in phase 1 studies. Single intramuscular or subcutaneous injections maintained stable drug levels for prolonged periods, supporting ultra long-acting (ULA) dosing intervals of up to six months. The treatment was generally well tolerated, with the most common adverse effects being mild to moderate injection site reactions and no serious adverse events or study withdrawals due to side effects. “Our R&D efforts are built around delivering best-in-class, long-acting therapies that challenge the status quo and help make HIV treatment a smaller, less frequent part of people’s lives,” says Kimberly Smith, M.D., MPH, Head of Research & Development and Senior Vice President at ViiV Healthcare. Kimberly Smith, M.D., MPH, Head of Research & Development and Senior Vice President at ViiV Healthcare “The data we’re presenting on VH184, our third-generation INSTI, indicate a potential high barrier to resistance and twice-yearly dosing intervals. “Early results for VH499, a capsid inhibitor, point to its potential for dosing every six months. “These data underscore how ViiV Healthcare is working to define the future of HIV care through ultra long-acting options designed to address the needs and preferences of people living with HIV and will inform our plans to introduce the first INSTI-based, twice-yearly regimen for people with HIV.” Implications for future HIV care Together, VH184 and VH499 represent a shift toward longer-acting, less frequent HIV therapies. These early-stage results lay the groundwork for further clinical studies to optimise dosing schedules and confirm safety and efficacy in people living with HIV. As part of ViiV Healthcare’s broader pipeline, these agents underscore the company’s commitment to expanding treatment options that minimise the daily burden of HIV management and improve quality of life for patients. Company portals GSK ViiV Healthcare Executives Kimberly Smith Head of Research & Development and Senior Vice President