Findings from the HPTN 084 open label extension show maternal and pregnancy outcomes with Apretude (cabotegravir long-acting for PrEP) exposure were comparable to those with no cabotegravir exposure

HPTN 084开放标签扩展的结果显示，暴露于Apretude（cabotegravir长效PrEP）的孕妇和妊娠结局与未暴露于cabotegravir的孕妇相当

Pharmacokinetic findings demonstrated that target concentrations of cabotegravir were maintained above those associated with protection against HIV acquisition throughout the overall pregnancy period

药代动力学研究结果表明，在整个怀孕期间，卡博格雷韦的目标浓度保持在与预防艾滋病毒感染相关的浓度以上

GSK plc (LSE/NYSE: GSK) announced that ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, today shared new maternal safety and pregnancy outcomes and pharmacokinetic (PK) findings from the HIV Prevention Trials Network (HPTN) 084 open label extension (OLE) evaluating cis-gender women in sub-Saharan Africa who became pregnant while using Apretude (cabotegravir LA for PrEP) for HIV pre-exposure prophylaxis (PrEP).

葛兰素史克股份有限公司（伦敦证交所/纽约证交所：葛兰素史克）宣布，由葛兰素史克控股的全球专业艾滋病毒公司ViiV Healthcare，辉瑞和Shionogi作为股东，今天分享了HIV预防试验网络（HPTN）084开放标签扩展（OLE）的新孕产妇安全性和妊娠结局以及药代动力学（PK）研究结果，该网络评估了撒哈拉以南非洲的cis性别女性，这些女性在使用Apretude（cabotegravir LA for PrEP）进行HIV暴露前预防（PrEP）时怀孕。

The findings showed that cabotegravir LA for PrEP was generally well tolerated among pregnant women, and PK findings demonstrated that cabotegravir levels were maintained above those associated with HIV protection throughout the overall pregnancy period.1,2 These data will be presented at the 25th International AIDS Conference being held in Munich, Germany (22 – 26 July).

。

.

.

Kimberly Smith, MD, MPH, Head of Research & Development at ViiV Healthcare, said: “Today’s late-breaking pregnancy safety data from the HPTN 084 open label extension add to the body of evidence for Apretude as a prevention option for women, including those who conceive while on this long-acting regimen.

ViiV Healthcare研发负责人、医学博士金伯利·史密斯（Kimberly Smith）表示：“今天来自HPTN 084开放标签扩展的晚期妊娠安全数据增加了大量证据，证明Apretude是女性的一种预防选择，包括那些在这种长效方案下怀孕的女性。

Women continue to tell us they need more options for HIV prevention, which is why we have been focused on studying cabotegravir LA for PrEP in women from the very beginning. We will continue to prioritise their needs, and those of others disproportionately affected by HIV, as part of our ongoing commitment to ending the epidemic.”.

女性继续告诉我们，他们需要更多的艾滋病毒预防选择，这就是为什么我们从一开始就专注于研究cabotegravir LA用于女性PrEP的原因。我们将继续优先考虑他们的需求，以及其他受艾滋病毒影响较大的人的需求，作为我们持续致力于结束这一流行病的一部分。”。

The original findings of HPTN 084 reported that cabotegravir LA for PrEP showed superior efficacy to daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) tablets at reducing the risk of acquisition of HIV in women.3 Participants who entered the HPTN 084 OLE (n=2472) were able to choose cabotegravir LA for PrEP or FTC/TDF tablets as PrEP, and contraceptive requirements were removed.

HPTN 084的原始研究结果报告说，用于PrEP的卡博格雷韦LA在降低女性感染艾滋病毒的风险方面显示出优于每日口服恩曲他滨/富马酸替诺福韦二酯（FTC/TDF）片剂的疗效。3进入HPTN 084 OLE的参与者（n=2472）能够选择卡博格雷韦LA用于PrEP或FTC/TDF片剂作为PrEP，并且避孕要求被删除。

Those with prior or current cabotegravir LA for PrEP exposure at the time of pregnancy could consent to continue injections throughout pregnancy. Maternal safety and pregnancy outcomes were assessed across the 367 confirmed pregnancies in 348 participants. .

那些在怀孕时曾或目前接触过cabotegravir LA的PrEP患者可以同意在整个怀孕期间继续注射。对348名参与者的367例确诊妊娠进行了孕产妇安全和妊娠结局评估。

The HPTN 084 OLE findings showed that cabotegravir LA for PrEP maternal and pregnancy outcomes were consistent across cabotegravir LA for PrEP and FTC/TDF exposure groups and with the expected background rates. Pregnancy-related maternal adverse event incidence was 45.7 (95% CI 33.1-61.6), 47.1 (95% CI 20.3-92.7), and 37.5 (95% CI 13.8-81.6) per 100 person years among those using cabotegravir LA for PrEP during pregnancy, prior to pregnancy, or with no cabotegravir LA for PrEP exposure, respectively.

HPTN 084 OLE研究结果显示，卡博格雷韦LA对PrEP和FTC/TDF暴露组的孕产妇和妊娠结局的影响与卡博格雷韦LA的预期背景率一致。在怀孕期间，怀孕前或没有使用卡博格雷韦LA进行PrEP暴露的患者中，与妊娠相关的母亲不良事件发生率分别为每100人年45.7（95%CI 33.1-61.6），47.1（95%CI 20.3-92.7）和37.5（95%CI 13.8-81.6）。

Adverse pregnancy outcome rates were similar across groups, with 33% (70/212) using cabotegravir LA for PrEP during pregnancy, 38% (26/68) having prior cabotegravir LA for PrEP use, and 27% (12/45) never using cabotegravir LA for PrEP reporting a negative outcome. One major congenital anomaly was observed and no maternal deaths were recorded.

各组不良妊娠结局率相似，33%（70/212）在怀孕期间使用卡博格雷韦LA进行PrEP，38%（26/68）先前使用卡博格雷韦LA进行PrEP，27%（12/45）从未使用卡博格雷韦LA进行PrEP报告阴性结果。观察到一个主要的先天性异常，没有孕产妇死亡的记录。

None of the women who became pregnant acquired HIV during pregnancy..

怀孕的妇女在怀孕期间都没有感染艾滋病毒。。

Sinead Delany-Moretlwe, MBBCh, Ph.D., DTM&H, HPTN 084 Protocol Chair, and Research Director at Wits RHI, University of the Witwatersrand in Johannesburg, South Africa, said: “Women of childbearing age in sub-Saharan Africa experience disproportionately higher rates of HIV incidence, making it essential that we study how HIV medicines impact their health and wellbeing during pregnancy.

MBBCh博士、DTM＆H、HPTN 084协议主席、南非约翰内斯堡威特沃特斯兰德大学Wits RHI研究主任Sinead Delany Moretlwe说：“撒哈拉以南非洲的育龄妇女艾滋病毒发病率过高，因此我们必须研究艾滋病毒药物如何影响怀孕期间的健康和福祉。

The findings of the HPTN 084 open label extension provide further evidence on the safety and tolerability of cabotegravir LA for PrEP in expectant mothers and their unborn infants while maintaining protective levels against HIV throughout pregnancy. These findings build upon the well-established efficacy of cabotegravir LA for PrEP and provide reassurance for its usage in this particularly vulnerable population.”.

HPTN 084开放标签扩展的研究结果进一步证明了卡博特格雷韦LA对孕妇及其未出生婴儿PrEP的安全性和耐受性，同时在整个怀孕期间保持了对HIV的保护水平。这些发现建立在cabotegravir LA对PrEP的公认疗效的基础上，并为其在这个特别脆弱的人群中的使用提供了保证。”。

The sub-study PK analysis of the HPTN 084 OLE included 50 participants who continued to receive cabotegravir LA for PrEP prior to and during pregnancy. The study found that concentrations of cabotegravir were comparable between the pre-pregnant, pregnant and post-partum periods (median Ctrough concentrations were 2.1 µg/mL [IQR: 1.3, 2.7], 1.9 µg/mL [IQR: 1.5, 2.2], and 2.5 µg/mL [IQR: 2.0, 3.5], respectively).

HPTN 084 OLE的子研究PK分析包括50名参与者，他们在怀孕前和怀孕期间继续接受cabotegravir LA进行PrEP。该研究发现，卡博特拉韦的浓度在孕前，妊娠期和产后相当（中位Ctrough浓度分别为2.1µg/mL[IQR:1.3、2.7]，1.9µg/mL[IQR:1.5、2.2]和2.5µg/mL[IQR:2.0、3.5]）。

Although cabotegravir LA for PrEP concentrations declined from the first trimester through to the third trimester of pregnancy (median Ctrough concentrations during the first, second and third trimesters were 2.5 µg/mL [IQR: 2.0, 3.2], 1.8 µg/mL [IQR: 1.5, 2.2], and 1.6 µg/mL [IQR: 1.3, 2.2], respectively), 100% of Ctrough concentrations during the first and second trimesters, and 98% of Ctrough concentrations during the third trimester, remained above target thresholds for the medicine.

虽然cabotegravir LA的PrEP浓度从妊娠早期到妊娠晚期下降（妊娠早期，中期和晚期的中位Ctrough浓度分别为2.5µg/mL[IQR:2.0，3.2]，1.8µg/mL[IQR:1.5，2.2]和1.6µg/mL[IQR:1.3，2.2]），但妊娠早期和中期的Ctrough浓度为100%，妊娠晚期的Ctrough浓度为98%，仍高于药物的目标阈值。

These data indicate dose modifications are unlikely to be required for women who become pregnant, although additional analyses are forthcoming to supplement these findings..

这些数据表明，怀孕的女性不太可能需要调整剂量，尽管即将进行额外的分析来补充这些发现。。

Apretude (cabotegravir LA for PrEP) is approved for use in multiple countries including the US, EU, UK, Canada, Australia and South Africa. Submission to other regulatory agencies is on-going.

Apretude（cabotegravir LA for PrEP）被批准在多个国家使用，包括美国、欧盟、英国、加拿大、澳大利亚和南非。正在向其他监管机构提交。

About HPTN 084 (NCT03164564)3,4

关于HPTN 084（NCT03164564）3,4

The HPTN 084 trial is a phase III double blind superiority trial designed to evaluate the safety and efficacy of the long-acting injectable cabotegravir for HIV prevention administered every eight weeks compared to daily oral TDF/FTC tablets (200 mg/300 mg) in 3,224 cisgender women who are at increased risk of HIV acquisition.

HPTN 084试验是一项III期双盲优越性试验，旨在评估每八周服用一次长效注射卡博格雷韦预防艾滋病毒的安全性和有效性，与每日口服TDF/FTC片剂（200 mg/300 mg）相比，3224名女性感染艾滋病毒的风险增加。

The trial design included an oral lead-in phase to assess tolerability to cabotegravir before administering the IM injection. HPTN 084 opened to enrolment in November 2017 and is being conducted at research centres in Botswana, Kenya, Malawi, South Africa, Eswatini, Uganda, and Zimbabwe..

试验设计包括口服导入阶段，以在注射IM之前评估对卡博格雷韦的耐受性。HPTN 084于2017年11月开放招生，目前正在博茨瓦纳、肯尼亚、马拉维、南非、埃斯瓦蒂尼、乌干达和津巴布韦的研究中心进行。。

Cabotegravir long-acting was found to be superior to daily oral FTC/TDF in preventing HIV acquisition in the trial population. The most common adverse reactions (all grades) observed in at least 1% of participants receiving cabotegravir long-acting were injection site reactions, diarrhoea, headache, fatigue, sleep disorders, nausea, dizziness, abdominal pain, vomiting, myalgia, and rash..

发现Cabotegravir长效剂在预防试验人群中HIV感染方面优于每日口服FTC/TDF。在接受卡波替格雷韦长效治疗的参与者中，至少有1%观察到最常见的不良反应（所有级别）是注射部位反应，腹泻，头痛，疲劳，睡眠障碍，恶心，头晕，腹痛，呕吐，肌痛和皮疹。。

HPTN 084 was jointly funded by the U.S. National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Mental Health (NIMH), the Bill & Melinda Gates Foundation and ViiV Healthcare and was conducted by the NIH-funded HPTN. Study product was provided by ViiV Healthcare and Gilead Sciences. .

HPTN 084由美国国立卫生研究院（National Institutes of Health）的National Institutes of Allergy and Infectious Diseases（NIAID）和National Institute of Mental Health（NIMH），Bill＆Melinda Gates Foundation和ViiV Healthcare共同资助，由NIH资助的HPTN进行。研究产品由ViiV Healthcare和Gilead Sciences提供。。

For further information please see https://clinicaltrials.gov/ct2/show/NCT03164564.

有关更多信息，请参阅https://clinicaltrials.gov/ct2/show/NCT03164564.

About Apretude

关于欣赏

Apretude is a medicine used for preventing sexually transmitted HIV-1 infection (pre-exposure prophylaxis or PrEP) in adults and adolescents weighing at least 35 kg who are at high risk of being infected. It should be used in combination with safer sex practices, such as using condoms. Apretude contains the active substance cabotegravir. .

Apretude是一种用于预防性传播HIV-1感染（暴露前预防或PrEP）的药物，用于预防体重至少35公斤且感染风险高的成年人和青少年。它应该与更安全的性行为相结合，例如使用避孕套。Apretude含有活性物质cabotegravir。。

Please consult the full Summary of Product Characteristics for all the safety information: Apretude 600 mg prolonged-release suspension for injection

有关所有安全信息，请参阅产品特性的完整摘要：注射用600 mg缓释混悬液

Trademarks are owned by or licensed to the ViiV Healthcare group of companies.

商标由ViiV Healthcare group of Companys拥有或授权。

About ViiV Healthcare

关于ViiV医疗

ViiV Healthcare is a global specialist HIV company established in November 2009 by GSK (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV and for people who are at risk of acquiring HIV. Shionogi became a ViiV shareholder in October 2012.

ViiV Healthcare是由葛兰素史克（LSE:GSK）和辉瑞（NYSE:PFE）于2009年11月成立的一家全球专业HIV公司，致力于为艾滋病毒感染者和有感染艾滋病毒风险的人提供治疗和护理方面的进步。Shionogi于2012年10月成为ViiV股东。

The company’s aims are to take a deeper and broader interest in HIV and AIDS than any company has done before and take a new approach to deliver effective and innovative medicines for HIV treatment and prevention, as well as support communities affected by HIV. For more information on the company, its management, portfolio, pipeline, and commitment, please visit viivhealthcare.com. .

该公司的目标是比以往任何公司都对艾滋病毒和艾滋病产生更深入和更广泛的兴趣，并采取新的方法提供有效和创新的艾滋病毒治疗和预防药物，以及支持受艾滋病毒影响的社区。有关公司、管理层、投资组合、渠道和承诺的更多信息，请访问viivhealthcare.com。

About GSK

GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.

。更多信息请访问gsk.com。

Cautionary statement regarding forward-looking statements

关于前瞻性声明的警示声明

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in GSK’s Annual Report on Form 20-F for 2023, and GSK’s Q1 Results for 2024..

葛兰素史克提醒投资者，葛兰素史克所作的任何前瞻性陈述或预测，包括本公告中所作的前瞻性陈述或预测，都存在风险和不确定性，可能导致实际结果与预测结果产生重大差异。这些因素包括但不限于葛兰素史克2023年20-F表年度报告第3.D项“风险因素”中所述的因素，以及葛兰素史克2024年第一季度的业绩。。

References

参考文献

Delany-Moretlwe S, Voldal E, Saidi F, et al. Initial evaluation of CAB-LA Safety during pregnancy in the HPTN 084 open-label extension. Presented at the 25th International AIDS Conference. July 2024.

Delany Moretlwe S，Voldal E，Saidi F等。HPTN 084开放标签扩展中怀孕期间CAB-LA安全性的初步评估。在第25届国际艾滋病会议上发表。2024年7月。

Marzinke M, Voldal E, Hansom B, et al. Evaluation of Long-Acting Cabotegravir (CAB-LA) Pharmacokinetics During Pregnancy: A Sub-Study Analysis of the HPTN 084 Open Label Extension. Presented at the 25th International AIDS Conference. July 2024.

Marzinke M，Voldal E，Hansom B等。妊娠期长效卡博特格雷韦（CAB-LA）药代动力学的评估：HPTN 084开放标签扩展的子研究分析。在第25届国际艾滋病会议上发表。2024年7月。

Delaney-Moretlwe S, Hughes J, Bock P, et al. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. The Lancet 2022;399(10337):1779-1789. DOI: 10.1016/S0140-6736(22)00538-4.

Delaney Moretlwe S，Hughes J，Bock P等。Cabotegravir预防女性HIV-1：HPTN 084的结果，一项3期随机临床试验。柳叶刀2022；399（10337）：1779-1789年。DOI:10.1016/S0140-6736（22）00538-4。

Clinical Trials.gov - Evaluating the Safety and Efficacy of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women. Available at https://clinicaltrials.gov/ct2/show/ NCT03164564. Last accessed July 2024.

Clinical Trials.gov-评估长效注射用卡博格雷韦与每日口服TDF/FTC相比在未感染HIV的女性暴露前预防的安全性和有效性。可在https://clinicaltrials.gov/ct2/show/NCT03164564。上次访问时间为2024年7月。