Long-acting HIV Pre-Exposure Prophylaxis Integrated With Community-based Sexual and Reproductive Health in South Africa (LAPIS): A Hybrid (1a) Cluster Randomised Controlled Phase 3B Trial of Effectiveness and Implementation

The goal of this hybrid (1a) Cluster Randomised Controlled Trial phase 3B trial is to evaluate the effectiveness and implementation of offering a choice of HIV Pre-Exposure Products (PrEP) through community-based sexual and reproductive health services, on PrEP uptake and retention, and population prevalence of sexually transmissible HIV amongst adolescents and young adults living in rural South Africa.
Researchers will compare adding the choice of long-acting PrEP, i.e. two monthly injectable cabotegravir (CAB LA) or dapiravine vaginal ring and HIV post exposure prophylaxis packs to daily oral PrEP integrated with community-based SRH in the 20 intervention clusters with standard of care (SoC), daily oral PrEP integrated with community-based SRH in the 20 control clusters, on uptake and retention on PrEP. We hypothesise that offering a choice of long-acting or oral PrEP and PEP within the community-based delivery of SRH services will overcome the challenges and barriers to effective use of oral daily PrEP and lead to a population-level effect on uptake and retention on PrEP and thus the prevalence of sexually transmissible HIV amongst 15-30 year olds living in rural KwaZulu-Natal, South Africa.

开始日期2024-02-27

申办/合作机构-

NCT06807736

/ RecruitingN/AIIT

PrEPared to Choose (PtC): An Implementation Study of the Delivery of Cabotegravir Long-acting Injectable Pre-exposure Prophylaxis (PrEP) as an HIV Prevention Product Option Within a PrEP Choice Context in a Real World Setting in Cape Town.

The goal of this clinical trial is to offer adolescents and young people in Cape Town, South Africa different HIV pre-exposure prophylaxis (PrEP) products and describe how they use these products over an 18-month period. The study has both clinical and implementation primary aims. The primary clinical aim is short and long-term persistence on PrEP. Persistence is defined as the length of time that a participant shows continuous use of a PrEP product as intended, without stopping PrEP or switching to another PrEP product. The primary implementation aim involves the determination of factors that either enable or serve as a barrier to PrEP uptake and continuation.
Participants will be offered a choice between three antiretroviral-containing PrEP products: (1) a Tenofovir-based oral tablet that needs to be taken daily; (2) a vaginal ring containing Dapivirine that provides HIV protection for up to one month; and (3) an intramuscular injection containing Cabotegravir that provides HIV protection for up to two months. Participants will be able to use the same product throughout the study, switch between products, or stop and restart on PrEP at any point.
The study will be offered from two study sites: the first is a mobile clinic that rotates on a fixed schedule across the study area and the second is a fixed-location government primary healthcare clinic. The study will be open to confirmed HIV-negative individuals, including adolescent girls and young women (aged 15-29 years), young gender and sexually diverse populations aged 15-29 years (including men who have sex with men, transgender people, and non-binary people), and their collective sexual partners (including heterosexual, cisgender men) of any age.

开始日期2024-02-13

申办/合作机构

Desmond Tutu Hiv Foundation

[+2]

NCT05416021

/ Completed临床1期

A Phase I, Open-Label, Randomized, Crossover Trial to Investigate the Relative Bioavailability of the 25 mg Dapivirine Vaginal Ring-004 Inserted Every 30 Days and 100 mg DPV Ring-008 Inserted for 90 Days in Healthy Female Participants

A Phase I, Open-Label, Randomized, Crossover Trial to Investigate the Relative Bioavailability of the 25 mg Dapivirine Vaginal Ring-004 inserted every 30 days and 100 mg Dapivirine Vaginal Ring-008 inserted for 90 days in Healthy Female Participants

开始日期2022-08-01

申办/合作机构

INC Research Holdings, Inc.

100 项与 Dapivirine 相关的临床结果

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100 项与 Dapivirine 相关的转化医学

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100 项与 Dapivirine 相关的专利（医药）

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206

项与 Dapivirine 相关的文献（医药）

2026-10-20·Sexual Health

Changes in sexual behavior among women in studies evaluating the dapivirine vaginal ring for HIV prevention

Article

作者: Garcia, Morgan ; Siva, Samantha ; Palanee-Phillips, Thesla ; Jacobson, Cindy E. ; Neradilek, Moni ; Akello, Carolyne A. ; Hlahla, Kudzai ; Mansoor, Leila E. ; Reddy, Krishnaveni ; Gati, Brenda ; Mhlanga, Felix ; Singh, Nishanta ; Balkus, Jennifer E.

Background:

Access to novel HIV prevention technologies often raise concerns of risk compensation. This analysis examined changes in the sexual behaviors of MTN 020/ASPIRE participants, a placebo controlled randomized control trial, who subsequently enrolled in MTN-025/HOPE, an open-label extension using the dapivirine vaginal ring.

Methods:

Both studies enrolled healthy, sexually active, HIV-negative women from Malawi, South Africa, Uganda and Zimbabwe. Longitudinal data on participants’ sexual behaviors, specifically sex with a nonprimary partner (past 3 months), and use of male or female condoms at the last vaginal sex act were compared between ASPIRE and HOPE. Conditional and mixed ordinal logistic regression models evaluated associations between study and sexual behaviors at enrollment, and quarterly over the first 12 months.

Results:

Of the 2629 individuals enrolled in ASPIRE, 1456 (55%) participated in HOPE. At enrollment, the proportion of participants who reported sex with a nonprimary partner and condom use at last vaginal sex act did not differ by study. Across all quarterly follow-up visits, sex with a nonprimary partner was more common in HOPE (13.9–18.7%) than ASPIRE (10.7–12.6%); adjusted OR 1.47, 95% CI 1.24–1.75, P < 0.001. There was no difference in condom use at the last vaginal act across all quarterly follow-up visits between ASPIRE (36.5–42.7%) and HOPE (43.6–46.7%); adjusted OR 1.05, 95% CI 0.94–1.18.

Conclusion:

More women reported sex with nonprimary partners in HOPE, with little change in condom use over time between the two studies. Understanding behavior changes during PrEP use allows for tailored, holistic reproductive health programming.

2026-09-29·ACS Omega

Systematic Structure–Activity Relationship Investigation on Novel 5-Alkyl-6-benzyl-2-{[(methylthio/phenylthio)alkyl]thio}-pyrimidin-4(3 H )-ones Endowed with Potent Anti-HIV-1 Activity

Article

作者: Bavagnoli, Laura ; Bianchi, Elena ; Nawrozkij, Maxim B. ; Ivanov, Roman ; Rotili, Dante ; Mai, Antonello ; Ragno, Rino ; Crespan, Emmanuele ; Esté, José A. ; Fiorentino, Francesco ; Voronkov, Andrey ; Hailu, Gebremedhin Solomon ; Chernyshov, Vladimir ; Astolfi, Roberta ; Mancini, Andrea ; Golovina, Anastasia ; Fabbrizi, Emanuele ; Degtyarenko, Egor

Abstract:

Four series of 5-alkyl-6-benzyl-2-[(methylthio/phenylthio)alkyl]thiopyrimidin-4(3H)-ones were systematically diversified at C2, C5, and C6 and evaluated as anti-HIV-1 agents. In MT-4 cells, these compounds displayed low-to-moderate cytotoxicity and subnanomolar-to-submicromolar inhibition of WT HIV-1, with potency governed by a balanced SAR. Ortho-dihalogenated C6-benzyl groups, particularly 2,6-F2 and 2,6-Cl2, were generally favored. In the 2,6-dihalobenzyl series, optimal activity required C5 methyl combined with para-substituted phenylthiomethyl groups at C2, whereas 3,5-Me2-benzyl analogues benefited from C5 isopropyl paired with methylthioethyl (24l) or unsubstituted phenylthiomethyl (24m) C2 side chains. The p-methoxyphenylthiomethyl thiothymine derivatives 21e (2,6-F2) and 23e (2,6-Cl2) emerged as lead inhibitors, showing high selectivity, potent activity against WT and clinically relevant HIV-1 variants, superior efficacy compared with nevirapine and efavirenz, dapivirine-like potency, and improved resistance tolerance relative to phenethyl-S-DABO bioisosteres. Together, biological and QSAR and docking data contribute to defining optimization strategies aimed at achieving durable anti-HIV-1 activity within the investigated chemotype and support further development of next-generation NNRTIs with improved efficacy against clinically relevant HIV-1 strains.

2026-09-02·AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV

A qualitative exploration of women’s choices and experiences of using oral and vaginal HIV pre-exposure prophylaxis in Eswatini

Article

作者: Mmema, Nqobile ; Dlamini, Sinikiwe ; Ciglenecki, Iza ; Dlamini, Velibanti ; Wringe, Alison ; Daka, Michelle ; Kerschberger, Bernhard ; Flores, Antonio ; Lekelem, Skinner ; Mabhena, Edwin ; Mukooza, Esther ; Matse, Sindy

Understanding women's decision-making when offered different HIV pre-exposure prophylaxis (PrEP) options is critical for improving uptake. This qualitative study explored factors influencing PrEP choices among Swazi women in 2022-2023. In-depth interviews were conducted with 17 women who accepted or declined oral PrEP or the Dapivirine vaginal ring; and 6 healthcare workers who prescribed PrEP. One focus group discussion (FGD) with eight women eligible for PrEP and three FGDs with six to eight male community members explored attitudes to PrEP. Data were collected in Siswati, transcribed into English, and analyzed thematically. Women's decisions around PrEP use and product preferences were shaped by social norms around sexual relationships, practicalities of use and perceptions of effectiveness. Many preferred "invisible" methods, such as the ring, to avoid stigma or partner violence, while oral PrEP was favored by some women practicing anal sex. Ease of adherence, side-effects and ring insertion practicalities also influenced choices. Some participants questioned PrEP effectiveness or feared it might spread HIV, while some healthcare workers noted that future injectable options could reduce blame in cases of seroconversion. The findings highlight the need to offer women a range of PrEP options, supported by accurate information, to expand coverage in high-incidence settings.

项与 Dapivirine 相关的新闻（医药）

2026-09-08

·生息致知

第三十二章：生物药物：多肽、蛋白质、核苷酸与大环内酯类药物

以下是书籍《Drug Design：From Structure and Mode-of-Action to Rational Design Concepts》中第三十二章：生物药物：多肽、蛋白质、核苷酸与大环内酯类药物（Biologicals: Peptides, Proteins, Nucleotides, and Macrolides as Drugs）的主要内容。本章系统综述了以生物大分子为药物核心的一类治疗策略，涵盖蛋白质/多肽类药物、单克隆抗体、反义寡核苷酸与mRNA药物、核苷/核苷酸类似物、分子楔形抑制剂以及大环内酯类抗生素等六大类生物药物的设计原理、作用机制与临床应用。文章从基因工程蛋白的生产出发，以胰岛素的结构改造为范例，深入阐述了单克隆抗体的制备与多种治疗策略（疫苗、化疗、受体拮抗、放射免疫治疗、抗体-药物偶联物），继而讨论了核酸类药物（反义寡核苷酸、mRNA疫苗）的化学修饰策略，介绍了核苷/核苷酸作为"假底物"抑制病毒复制的机制（如5-氟尿嘧啶、阿昔洛韦、AZT），以及分子楔形抑制剂（非核苷类RT抑制剂、喹诺酮类、四环素类）的作用原理，最后详细描述了大环内酯类抗生素靶向核糖体的多种作用模式与耐药机制。引言内源性生物分子（蛋白质、多肽、核酸等）在机体功能过程中扮演核心角色。外源小分子可用来调控这些过程，但直接将内源性生物分子本身作为药物使用，在某些疾病（如内源性物质分泌不足或功能异常）中同样具有巨大潜力。基因工程技术的出现使得选择性生产具有特定性质的多肽和蛋白质成为可能。然而，肽类和蛋白质类药物面临口服生物利用度低、稳定性差等挑战，通常需静脉给药。此外，抗体类药物因分子量大，无法穿透细胞膜，主要作用于细胞表面或细胞外物质。本章将围绕多类生物药物的设计策略，结合结构生物学与药物化学原理，系统阐述其作用机制与临床应用。32.1 基因工程技术生产蛋白质 • 内源性蛋白长期以来被用于替代疗法。早期使用动物胰腺提取物（猪胰岛素与人类仅差1个氨基酸，牛胰岛素差3个），但产量远不能满足需求。 • 血友病患者曾因使用凝血因子VIII而感染肝炎病毒和HIV，促使人们转向重组蛋白生产。 • 1982年，Eli Lilly率先将大肠杆菌生产的重组人胰岛素投入临床，随后生长激素、乙肝疫苗、组织纤溶酶原激活剂（tPA）、干扰素、促红细胞生成素（EPO）等相继问世。除细菌培养外，转基因动物（如荷兰的Herman公牛、产tPA的转基因绵羊）也被用于蛋白生产，大幅降低成本。此外，基因工程还广泛应用于抗体、疫苗、诊断酶及生物传感器等领域。32.2 胰岛素的定向改造 • 糖尿病由胰腺分泌的胰岛素不足引起。 • 胰岛素由A链（21个氨基酸）和B链（30个氨基酸）通过3个二硫键交联而成，是胰岛素受体的激动剂。通过定向改造可改善其药代动力学性质：-（1）在B链引入额外精氨酸（Arg B31），使等电点移向中性pH，降低溶解度，产生 depot 效应，实现长效作用；进一步优化晶体堆积后，可获得仅需每日一次给药的长效胰岛素类似物。-（2）Eli Lilly将B链倒数第二个和第三个氨基酸（Pro28和Lys29）互换，得到快速吸收、短效的胰岛素类似物，显著缩短了注射与进餐之间的时间间隔。32.3 单克隆抗体：疫苗、化疗药物与受体拮抗剂32.3.1 抗体的结构与功能 • 抗体（免疫球蛋白G，IgG）呈Y形结构，由两条轻链和两条重链通过二硫键连接。 • Fab区域（抗原结合区）包含可变区（VL、CL、VH、CH1），其末端有三个高变环（CDR），负责识别不同抗原。Fc区域（恒定区）与吞噬细胞结合，介导清除。 • 抗体可识别从小的磷酸胆碱到大的蛋白质（如溶菌酶，接触面积20×30 Å，涉及16-17个残基）等各种大小的抗原。32.3.2 单克隆抗体的制备 1975年Köhler和Milstein发明杂交瘤技术：将免疫动物脾脏中的抗体产生细胞与骨髓瘤细胞融合，获得可无限增殖的杂交瘤细胞。该技术获诺贝尔奖，但未申请专利。32.3.3 抗体的改造与人类化动物来源的抗体可引发免疫反应。通过嵌合蛋白技术（鼠源可变区+人源恒定区）和人源化技术（仅保留鼠源CDR区）可降低免疫原性。人源抗体还可通过转基因羊奶生产。32.3.4 抗体在疫苗中的应用基因工程疫苗无需整个病毒，只需表达病毒包膜蛋白的表面片段即可诱导抗体产生。乙肝疫苗即为此类代表。HIV疫苗因病毒高度变异、表面糖基化遮蔽而研发困难。32.3.5 抗体作为治疗药物 • 受体拮抗：西妥昔单抗（Cetuximab）靶向表皮生长因子受体（EGFR），阻断配体结合，抑制肿瘤细胞增殖信号，并标记肿瘤细胞供吞噬细胞清除。 • 免疫抑制：巴利昔单抗（Basiliximab）和达利珠单抗（Daclizumab）靶向T细胞IL-2受体α亚基，用于器官移植排斥的预防。 • 可溶性受体融合蛋白：依那西普（Etanercept/Enbrel®）将TNF-α受体胞外区与抗体Fc段融合，用于类风湿性关节炎和银屑病治疗。 • 放射免疫治疗：CD20抗体标记放射性核素（¹³¹I、⁹⁰Y等），通过螯合配体偶联至抗体，实现肿瘤局部放射治疗（如Tositumomab、Ibritumomab）。32.3.6 抗体-药物偶联物（ADC）将抗体与细胞毒性药物偶联，利用抗体的特异性识别将药物精准递送至肿瘤细胞。ADC通过受体介导的内吞作用进入细胞，在溶酶体中降解后释放药物，引发细胞凋亡。目前已有多种ADC获批上市，100多种处于临床试验阶段。32.4 反义寡核苷酸与mRNA作为药物32.4.1 反义寡核苷酸的作用原理通过设计与目标mRNA互补的寡核苷酸链（12-28个碱基），形成RNA-DNA双链，被RNase H降解或阻碍核糖体读取，从而抑制蛋白质合成。天然寡核苷酸极性大、带负电荷，无法穿透细胞膜，且易被核酸酶降解。32.4.2 化学修饰策略 • 磷酸骨架修饰：用硫原子替代氧原子，提高核酸酶稳定性（但降低与互补mRNA的复合能力）。 • 核糖修饰：2′-OH的甲基化或甲氧基乙基化可降低毒性并提高RNase H稳定性。 • 锁式核酸（LNA）：在核糖2′-OH与C4之间形成环醚，增强结合稳定性。 • 肽核酸（PNA）：用寡甘氨酸链替代磷酸-核糖骨架，具有高度生物稳定性和低毒性，但溶解度差。 • 嵌合结构：LNA/PNA与DNA/RNA寡聚体的嵌合体也被考虑。32.4.3 临床应用 • 局部给药：福米韦生（Fomivirsen/Vitravene®）治疗巨细胞病毒视网膜炎（1998年首个反义药物）。 • 系统给药：针对BCL-2蛋白mRNA的抗癌药物、针对TGF-β2的抗转移药物、治疗炎症性肠病和代谢综合征的药物。32.4.4 mRNA作为药物与疫苗 mRNA本身极不稳定，Katalin Karikó和Drew Weissman的关键突破在于用假尿苷替代尿苷，使mRNA不被免疫系统识别为外来物质，同时提高稳定性。2023年获诺贝尔奖。mRNA疫苗（如BioNTech、Moderna的COVID-19疫苗）将编码刺突蛋白的mRNA包裹在脂质纳米颗粒中，进入细胞后由核糖体翻译产生刺突蛋白，诱导体液免疫和细胞免疫。mRNA癌症疫苗通过提取患者肿瘤细胞的遗传信息，开发个性化疫苗，在恶性黑色素瘤和胶质母细胞瘤中取得进展。32.5 核苷与核苷酸作为假底物32.5.1 核苷酸类似物的抗肿瘤机制核苷由嘌呤/嘧啶碱基和戊糖组成，磷酸化后成为核苷酸。通过关键位置的化学修饰，使其被酶识别为正常底物但导致合成终止。 • 5-氟尿嘧啶（5-FU）：尿嘧啶5位H被F取代，被胸苷酸合酶识别后与Cys146共价结合，不可逆抑制酶活性。替加氟（Tegafur）为5-FU的前药，可口服。卡培他滨（Capecitabine）为多步激活的前药。 • 嘌呤类似物：6-巯基嘌呤（6-MP）、6-硫鸟嘌呤（6-TG）竞争性抑制嘌呤生物合成。氟达拉滨（Fludarabine）、克拉屈滨（Cladribine）、喷司他丁（Pentostatin）抑制腺苷脱氨酶，用于白血病治疗。32.5.2 抗病毒核苷类似物 • 阿昔洛韦（Acyclovir）：鸟苷类似物，五元糖环开环且缺少3′-OH。被病毒胸苷激酶磷酸化为单磷酸，再由内源激酶转为三磷酸，掺入DNA后链延伸终止。 • AZT（齐多夫定）：胸苷类似物，3′-OH被叠氮基取代，被磷酸化后掺入DNA导致链终止。1987年获批，是首个HIV-RT抑制剂。 • 替诺福韦（Tenofovir）：开链类似物，已带有末端磷酸基团，需转为三磷酸后发挥作用。32.5.3 HIV逆转录酶（RT）的结构与抑制 RT为p66/p51异二聚体，p66亚基呈"手掌-手指-拇指"结构。非核苷类逆转录酶抑制剂（NNRTIs）如奈韦拉平（Nevirapine）结合于手掌区疏水口袋，使酶锁定在开放构象，阻止RNA-DNA杂合链的接纳。通过结构引导的药物设计，开发了具有"适应性结合"特征的依曲韦林（Etravirine）和达匹韦林（Dapivirine），可适应多种突变，耐药性低。32.6 分子楔形抑制剂破坏蛋白质-核苷酸识别32.6.1 非核苷类逆转录酶抑制剂（NNRTI）的适应性结合奈韦拉平、TIBO、洛维雷德等结合于RT手掌区疏水口袋，呈蝴蝶状构象，锁定酶的开放构象。通过结构引导设计，在洛维雷德和吖啶/嘧啶片段中引入三嗪/嘧啶 moiety，发现结构相似的衍生物可采取完全不同的结合模式。利用这种"变色龙式"适应性结合，开发了依曲韦林（2008年获批），对多种突变株保持活性。32.6.2 喹诺酮类抗生素喹诺酮类靶向DNA旋转酶（拓扑异构酶II），催化细菌DNA超螺旋化。萘啶酸（1962年首个喹诺酮）的1-烷基-4-吡啶酮-3-羧酸骨架经优化得到环丙沙星（Ciprofloxacin）和莫西沙星（Moxifloxacin）。两个抗生素分子像楔形一样插入DNA断裂两端之间，阻止双链重新连接。6位氟取代基和7位碱性杂环的引入显著提高了活性。32.6.3 四环素类与Tet阻遏蛋白四环素与Tet阻遏蛋白结合后，像楔形一样插入阻遏蛋白的螺旋-转角-螺旋基序之间，使两个阅读基序间距从36 Å扩大到40 Å，无法正确读取DNA序列，阻遏蛋白从DNA上脱落，启动外排泵基因表达。这一特性被广泛应用于分子生物学中的基因表达调控。32.7 大环内酯类：微生物武器作为细胞抑制剂、抗真菌药、免疫抑制剂或抗生素32.7.1 大环内酯类的生物合成微生物通过非核糖体肽合成酶（NRPS）和聚酮合酶（PKS）途径合成复杂大环化合物。NRPS利用多种氨基酸和合成砌块，通过酰胺键和酯键形成大环；PKS则类似脂肪酸生物合成，以丙二酰辅酶A为起始原料。 32.7.2 大环内酯类的多种药理作用 • 免疫抑制：环孢素（Cyclosporine）与环孢素结合蛋白结合，抑制钙调磷酸酶活性，阻断IL-2合成，防止器官移植排斥。 • 抗真菌：制霉菌素、两性霉素B与真菌细胞膜中的麦角固醇结合，破坏膜完整性。 • 细胞毒性：rhizopodin等干扰肌动蛋白聚合，破坏细胞骨架。32.7.3 核糖体结构与功能核糖体是核糖核蛋白复合物（2/3 RNA + 1/3蛋白质），由大亚基（50S）和小亚基（30S）组成。小亚基负责解读遗传密码，大亚基负责肽键形成。核糖体本质上是核酶（ribozyme），催化功能由RNA执行。翻译过程涉及A位（氨基酰化tRNA）、P位（肽酰化tRNA）和E位（空tRNA退出）。肽基转移酶中心催化肽键形成。32.7.4 大环内酯类抗生素的作用机制红霉素（Erythromycin）是14元环大环内酯，结合于核糖体肽基转移酶中心附近的肽链出口隧道，阻止新生肽链延伸。克拉霉素（Clarithromycin）通过7-OH醚化提高酸稳定性；罗红霉素（Roxithromycin）通过10-羰基肟化提高稳定性；阿奇霉素（Azithromycin）将内酯环扩展为15元环并引入氮原子。32.7.5 耐药机制 A2058位腺嘌呤被鸟嘌呤取代（A→G突变）可导致红霉素活性下降五个数量级，因为鸟嘌呤的氨基与药物产生空间排斥。真核生物在此位置天然为鸟嘌呤，解释了14元大环内酯对细菌的选择性。32.7.6 链脲菌素的协同作用达福普司汀（Dalfopristin）和喹奴普汀（Quinupristin）分别结合于肽基转移酶中心和核糖体隧道入口，通过共享疏水接触面产生协同效应，联合使用对耐药菌的抑制效力比单独使用高16倍。两者以70:30比例混合为Synercid®，2000年获批用于耐药菌感染。总结本章全面综述了生物大分子类药物的设计原理与临床应用，涵盖了从蛋白质工程到核酸药物、从天然产物到合成药物的广泛策略。核心要点包括：（1）基因工程技术使重组蛋白药物的规模化生产成为可能，胰岛素的定向改造展示了结构导向药物设计的成功范例；（2）单克隆抗体凭借其高特异性，已成为肿瘤免疫治疗、自身免疫疾病治疗和靶向递送的核心工具；（3）反义寡核苷酸和mRNA药物代表了核酸药物的两大方向，化学修饰策略是克服其稳定性与递送瓶颈的关键；（4）核苷/核苷酸类似物通过"假底物"机制有效抑制病毒复制酶，是抗病毒和抗肿瘤治疗的重要基石；（5）分子楔形抑制剂通过空间插入破坏蛋白质-核酸识别，展示了结构生物学指导下的创新药物设计思路；（6）大环内酯类抗生素靶向核糖体，其协同作用机制和耐药机制的研究为克服耐药性提供了重要启示。总体而言，本章展示了现代药物设计如何深度融合结构生物学、分子生物学和化学合成技术，为开发新一代生物药物提供了坚实的理论基础和实践指导。关注「生息致知」，让AI与数学学习不迷路。

2026-05-19

·cidrz.org

CIDRZ CHEP Pays Courtesy Call on Central Province Health Office During Lenacapavir Training in Kabwe.

CIDRZ’s Controlling HIV Epidemic Project (CHEP) paid a courtesy call on the Central Province Health Office in Kabwe as part of ongoing activities related to the transitioning of the Zambia Integrated Health (ZIH) program, from Pact Inc. to CIDRZ. During the same period, CIDRZ, in collaboration with the Ministry of Health, is conducting a Trainer of Trainers (ToT) workshop focused on the rollout of pre-exposure prophylaxis (PrEP) products, namely, cabotegravir, Dapivirine Vaginal Ring (DVR) and Lenacapavir, a groundbreaking HIV prevention intervention described by experts as the closest alternative to an HIV vaccine. The PrEP workshop aims to equip frontline healthcare workers with the knowledge and skills required to effectively deliver the different PrEP products as Zambia strengthens efforts towards HIV epidemic control. The CHEP delegation was led by Ms Francheskie Vélez, Director of the Health Coordination Office at the U.S. Embassy in Zambia and included CHEP Chief of Party Dr Maurice Musheke. Speaking during the visit, Ms Vélez reaffirmed the U.S. Government’s commitment, through the U.S. Embassy in Zambia, to strengthening partnerships with local organisations to implement life-saving health interventions. She noted that CIDRZ had been identified as an ideal local partner as the U.S. Government shifts focus on prioritising local organisations to lead and sustain public health programmes. Ms Vélez also thanked the Provincial Health Office for hosting the team and supporting the successful implementation of the training programme in Kabwe. The Provincial Health Director, Dr Elijah Mutoloki, was represented by Dr Mwanja Kakusa, the Provincial Clinical Care Specialist for Central Province, who welcomed the delegation and expressed appreciation for selecting Kabwe as the host district for the training. Dr Kakusa noted that the Training of Trainers workshop was particularly important because Central Province had not been included in the previous training. She added that the healthcare workers participating in the training would play a critical role in cascading the knowledge and skills acquired to other healthcare workers across the province. Dr Kakusa further stated that the training would strengthen the province’s HIV response by enhancing healthcare workers’ capacity to deliver innovative HIV prevention services as the province seeks to achieve epidemic control. CIDRZ continues to work closely with the Ministry of Health, the U.S. Government through the U.S. Embassy in Zambia, and other partners to support evidence-based interventions that improve health outcomes and advance Zambia’s HIV response.

临床研究

2026-04-22

·cidrz.org

CIDRZ, Ministry of Health Train HIV Specialists in Advanced PrEP Delivery to Strengthen Prevention Efforts.

To strengthen HIV prevention efforts, the Controlling HIV Epidemic Project (CHEP), under the Centre for Infectious Disease Research in Zambia (CIDRZ), in collaboration with the Ministry of Health and with financial support from the United States Department of State, conducted a six-day Training of Trainers (ToT) workshop on the delivery of different pre-exposure prophylaxis (PrEP) products. The training which was held in Ndola, brought together HIV healthcare specialists from CIDRZ, the Copperbelt Provincial Health Office, Ndola Teaching Hospital, Copperbelt District Health Offices, and the United States Department of State. Participants were drawn from Eastern, Western, Lusaka, and Copperbelt provinces. The training was officially opened by Copperbelt Provincial Health Director, Dr Charles Mwinuna, and focused on equipping participants with the skills required to deliver combination HIV prevention services. Particular emphasis was placed on oral PrEP, Cabotegravir (2-month injectable PrEP), Lenacapavir (6-month injectable PrEP), and the Dapivirine Vaginal Ring (DVR), a long-acting, user-controlled PrEP product designed to reduce the risk of acquiring HIV during vaginal sex. Meanwhile, Dr Paul Mwale, Copperbelt Provincial Advanced HIV Disease (AHD) and Injectable PrEP Coordinator under the Ministry of Health, led a session outlining the mandate of the HIV Prevention Programme, which aims to achieve epidemic control and end AIDS by 2030. He highlighted national targets, including reducing new HIV infections from 28,000 to 15,000 by 2026 and increasing PrEP uptake among key and priority populations to 220,000 annually, emphasising the need for accelerated efforts to meet both national and global goals. In another session, Dr Monica Chibesakunda, CIDRZ’s HIV Testing and Prevention Lead, trained participants on HIV testing services, stressing their role in both preventing new infections and linking individuals to care. She emphasised adherence to national HIV testing guidelines for PrEP initiation and the importance of providing tailored prevention services based on individual risk. Other sessions covered demand generation for PrEP, scheduling PrEP clinical visits, managing beneficiaries who missed appointments, switching beneficiaries between PrEP products, pharmacovigilance, and comprehensive data documentation. The training also addressed the link between Gender-Based Violence (GBV), Intimate Partner Violence (IPV), and HIV risk. Facilitators underscored the importance of integrating GBV and IPV screening into HIV services to support comprehensive, client-centred care. The workshop concluded with participants committing to cascade the knowledge gained and strengthen HIV prevention services, contributing to Zambia’s goal of ending AIDS as a public health threat by 2030.

临床研究

100 项与 Dapivirine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11246	Dapivirine	G01AX17	DB08639

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床3期	肯尼亚	INC Research Holdings, Inc.	2011-07-01
HIV感染	临床3期	肯尼亚	International Partnership for Microbicides	2011-07-01
HIV感染	临床3期	马拉维	INC Research Holdings, Inc.	2011-07-01
HIV感染	临床3期	卢旺达	INC Research Holdings, Inc.	2011-07-01
HIV感染	临床3期	卢旺达	International Partnership for Microbicides	2011-07-01
HIV感染	临床3期	南非	INC Research Holdings, Inc.	2011-07-01
HIV感染	临床3期	津巴布韦	INC Research Holdings, Inc.	2011-07-01
获得性免疫缺陷综合征	临床2期	南非	INC Research Holdings, Inc.	2009-07-01
获得性免疫缺陷综合征	临床2期	南非	International Partnership for Microbicides	2009-07-01
避孕	临床1期	美国	International Partnership for Microbicides	2018-07-17

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03965923 (MTN-042/DELIVER, Pubmed \| Lancet HIV)	临床3期	HIV感染	251	Dapivirine vaginal ring	顧壓網醖獵淵鹹淵蓋選(製蓋鹽夢獵觸糧觸繭醖) = 製顧製鬱窪製艱蓋鏇衊夢膚網獵壓鏇選醖選襯 (獵鑰糧齋醖蓋顧襯鑰醖 ) 更多	积极	2026-03-01
NCT03965923 (MTN-042/DELIVER, Pubmed \| Lancet HIV)	临床3期	HIV感染	545	Dapivirine vaginal ring	襯遞襯鹽鹹觸艱鏇製遞(積鏇鑰製鏇鑰繭範夢鑰) = 範製窪鹹築憲鹽築簾積醖積齋獵糧選鏇簾遞範 (餘願壓糧膚膚顧襯蓋鹹 ) 更多	积极	2025-11-01
				Oral PrEP (tenofovir disoproxil fumarate plus emtricitabine)	襯遞襯鹽鹹觸艱鏇製遞(積鏇鑰製鏇鑰繭範夢鑰) = 築鏇顧襯窪築鑰憲鬱築醖積齋獵糧選鏇簾遞範 (餘願壓糧膚膚顧襯蓋鹹 ) 更多
NCT04140266 (MTN-043, Pubmed \| Lancet HIV)	临床3期	母乳喂养	197	Dapivirine vaginal ring (DVR)	齋夢範壓遞網膚鏇糧願(構膚餘齋窪夢願蓋積鹽) = 醖齋鏇獵網顧構廠積壓鏇膚鬱餘壓憲廠遞網衊 (簾構願簾獵網齋膚鬱製 )	积极	2025-03-01
IAS2024	临床2期	HIV感染	60	Truvada	鏇艱獵餘築廠製繭艱願(廠齋鬱網鏇窪鏇網鬱夢) = 廠範齋淵構鬱築製構齋齋獵願繭獵鹽築遞壓襯 (艱廠繭簾觸襯夢衊廠夢 )	积极	2024-07-22
				Dapivirine ring	鏇艱獵餘築廠製繭艱願(廠齋鬱網鏇窪鏇網鬱夢) = 範積繭簾蓋夢壓齋壓製齋獵願繭獵鹽築遞壓襯 (艱廠繭簾觸襯夢衊廠夢 )
MTN-042/DELIVER (IAS2024)	临床3期	HIV感染	154	Dapivirine Vaginal Ring	窪衊繭鹹艱遞鬱廠夢艱(簾網壓鏇膚鹹構觸鏇膚) = 窪顧淵艱鬱壓醖壓網齋鹽遞襯遞遞糧衊齋觸觸 (積製簾醖襯糧顧遞築顧 )	不佳	2024-07-22
				Truvada	窪衊繭鹹艱遞鬱廠夢艱(簾網壓鏇膚鹹構觸鏇膚) = 餘糧蓋醖範製鹹糧鹹選鹽遞襯遞遞糧衊齋觸觸 (積製簾醖襯糧顧遞築顧 )
NCT01617096 (MTN-020/ASPIRE, Pubmed \| J Infect Dis)	临床3期	HIV感染	-	Dapivirine Vaginal Ring	製鹽廠繭壓膚網鬱製憲(獵網醖鹽鏇顧獵艱憲廠) = 衊鬱廠艱壓憲壓齋蓋淵製淵觸艱蓋壓蓋遞遞積 (構鑰膚衊糧獵餘壓築鏇, 1.8 ~ 3.1)	积极	2024-04-12
				Placebo	製鹽廠繭壓膚網鬱製憲(獵網醖鹽鏇顧獵艱憲廠) = 醖艱鏇膚廠廠鹽築鹽製製淵觸艱蓋壓蓋遞遞積 (構鑰膚衊糧獵餘壓築鏇, 2.9 ~ 4.4)
NCT01539226 (The Ring Study, Pubmed \| BMJ Open) 人工标引	N/A	HIV感染	197	Dapivirine vaginal ring / placebo vaginal ring	顧獵艱繭襯顧遞築鏇鑰(鑰簾餘獵廠鏇廠窪窪窪) = 鑰網鬱糧遞壓襯獵糧衊築積窪獵窪觸獵遞積齋 (網獵繭淵襯襯製餘願淵, 44.7 ~ 60.3) 更多	不佳	2024-04-08
				Dapivirine vaginal ring	顧獵艱繭襯顧遞築鏇鑰(鑰簾餘獵廠鏇廠窪窪窪) = 範窪製鏇築選網鹽衊積築積窪獵窪觸獵遞積齋 (網獵繭淵襯襯製餘願淵 )
NCT01617096 (MTN-020/ASPIRE \| ASPIRE \| MTN-020, CTgov)	临床3期	HIV感染	2,629	Dapivirine Vaginal Ring (Dapivirine Vaginal Ring)	廠衊積憲積鬱選憲壓獵 = 觸鑰構製襯廠繭夢鹽夢蓋壓鬱餘夢簾齋餘醖艱 (淵夢選艱顧膚齋願願選, 鑰壓廠顧繭餘窪餘淵糧 ~ 鹽鬱蓋繭範壓蓋製鏇繭) 更多	-	2022-12-16
				Placebo Ring (Placebo Ring)	廠衊積憲積鬱選憲壓獵 = 齋獵積顧壓夢淵淵衊鑰蓋壓鬱餘夢簾齋餘醖艱 (淵夢選艱顧膚齋願願選, 醖壓廠餘壓壓餘獵鬱簾 ~ 衊膚糧繭顧願夢構繭築) 更多
NCT02862171 \| NCT01539226 (The Ring Study and DREAM, Pubmed)	临床3期	HIV感染	-	Dapivirine Vaginal Ring-004 (DVR)	餘網鬱鬱鹽簾鹹蓋鹽艱(願鹽遞築築膚廠網製齋) = 鬱鬱獵廠齋壓觸築廠築選範遞構窪鹹遞鑰醖獵 (獵醖鏇窪鏇襯襯鏇艱鬱 )	-	2022-11-08
NCT02858037 (HOPE, CTgov)	临床3期	HIV感染	1,456	Dapivirine Vaginal Ring	艱窪鏇遞簾鏇衊艱淵衊 = 襯壓顧憲鹹觸鏇獵繭膚糧衊淵夢築廠鬱膚築選 (選艱積獵築夢鬱壓網鏇, 築窪鹹顧廠製願淵鹽簾 ~ 憲淵糧繭鏇顧築襯鬱網) 更多	-	2022-10-25