Co-benefits of co-delivery of long-acting antiretrovirals and contraceptives

长效抗逆转录病毒药物和避孕药联合给药的协同效益

基本信息

批准号：
10393063
负责人：
Rena Chiman Patel
金额：
$ 69.37万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-14 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10393063
关键词：
Address Adherence Africa South of the Sahara Age Anti-Retroviral Agents Behavioral Caring Clinic Clinical Contraceptive Agents Contraceptive methods Data Development Drug Interactions Drug Kinetics Etonogestrel Evaluation Face Female Adolescents Focus Groups Formulation Fostering Foundations Goals Guidelines HIV Health Health Benefit Health system Hybrids Individual Infusion procedures Injectable Intervention Interview Investigation Investments Kenya Learning Levonorgestrel Maternal Mortality Medroxyprogesterone 17-Acetate Methods Mother-to-child HIV transmission Oral Participant Patients Pharmaceutical Preparations Pharmacology Plasma Pregnancy Prevention Provider Public Health Randomized Readiness Regimen Research Resource-limited setting Resources Sampling Sentinel Structure Surveys Thinking Treatment outcome Viral Visit Work adherence rate antiretroviral therapy arm base cohort compliance behavior effectiveness implementation design effectiveness implementation trial effectiveness outcome effectiveness-implementation randomized trial hormonal contraception implementation outcomes implementation trial improved individualized medicine interest maternal morbidity novel open label preference pregnancy prevention primary outcome social stigma standard of care treatment arm treatment planning treatment program unintended pregnancy uptake young woman

项目摘要

PROJECT SUMMARY The first complete long-acting (LA) formulation of an antiretroviral therapy (ART), injectable cabotegravir and rilpivirine, is at the cusp of clinical approval—this is a potential game-changing development in the HIV treatment field. LA ART regimens increase options for patients and providers to improve patient adherence and persistence to treatment. Several subpopulations, including adolescent girls and young women (AGYW, ages 15-24), lag behind the 3rd 90-90-90 UNAIDS goal of viral suppression, including in Kenya. AGYW living with HIV (AGYWLHIV) face unique challenges in persistence to ART, and LA ART options have the potential to help overcome some of these challenges through greater confidentiality and reduced stigma compared to oral ART. Another major threat to AGYW’s health is unintended pregnancies, and AGYWLHIV also face unique challenges in uptake and continuation rates of LA contraceptives. More recently, the use of LA contraceptives, which include injectable and implantable methods, has gained marked momentum in Kenya, where many HIV treatment programs have integrated contraceptive provision into routine HIV care including for AGWY. Furthermore, AGYWLHIV are highly interested in co-delivery of ART and contraceptives. However, co-delivery also raises potential issues, both pharmacological and behavioral, that require further investigation. We propose foundational pharmacokinetic (PK) and qualitative studies leading up to a hybrid type I effectiveness-implementation trial randomizing individual AGYWLHIV to receive LA injectable cabotegravir/rilpivirine vs. standard of care in Kenya. Our central premise is that use of LA ART will foster long- term thinking for health, including for pregnancy prevention, and that leveraging existing LA contraceptive delivery platform will make LA ART highly feasible. Aim 1a will determine if combined injectable cabotegravir/rilpivirine use has any bidirectional drug-drug interactions with injectable or implantable contraceptives. Method: Parallel group PK evaluation with repeat plasma sampling among cabotegravir/rilpivirine users initiating injectable or implantable contraceptives vs. those not using any hormonal contraceptives (total 5 groups, n=21 per group). Aim 1b will qualitatively explore points of convergence and divergence, preferences and values, and health systems readiness around wider-scale co-delivery of LA ART/contraceptives. Method: 20-40 serial, semi-structured, in-depth interviews with AGYW from above sentinel cohort, and 2-4 focus group discussions with providers, policymakers, and stakeholders. Aim 2 will evaluate the impact of co-delivery of LA ART and contraceptives among AGYWLHIV via a hybrid trial on: (a) effectiveness outcomes of HIV treatment (viral suppression [primary outcome] and adherence/persistence) and contraception (uptake and continuation rates), and (b) implementation outcomes of acceptability, feasibility, and fidelity. Method: Open label, clinic- provided, mixed methods hybrid trial, randomizing AGYW 1:1 to switch to injectable cabotegravir/rilpivirine (intervention arm) vs. to continue to their current oral ART regimen (control arm; total n=550).

项目概要第一个完整的长效（LA）抗逆转录病毒疗法（ART）制剂，注射用卡博特韦和利匹韦林，正处于临床批准的风口浪尖——这是艾滋病毒领域潜在的改变游戏规则的发展 LA ART 方案为患者和提供者提供了更多选择，以提高患者的依从性和一些亚人群，包括少女和年轻女性（AGYW，年龄） 15-24），落后于联合国艾滋病规划署的第三个 90-90-90 病毒抑制目标，包括感染艾滋病毒的肯尼亚 AGYW。 (AGYWLHIV) 在坚持 ART 方面面临着独特的挑战，而 LA ART 选择有可能提供帮助与口服抗逆转录病毒治疗相比，通过更高的保密性和减少耻辱来克服其中一些挑战。 AGYW 健康的另一个主要威胁是意外怀孕，AGYWLHIV 也面临着独特的 LA 避孕药具的使用率和继续使用率方面面临的挑战最近，LA 避孕药具的使用，其中包括注射和植入方法，在肯尼亚取得了显着的势头，那里有许多艾滋病毒感染者治疗方案已将避孕措施纳入常规艾滋病毒护理中，包括 AGWY。此外，AGYWLHIV 对 ART 和避孕药具的共同交付非常感兴趣。还提出了需要进一步研究的药理学和行为方面的潜在问题。我们提出了基础药代动力学 (PK) 和定性研究，以形成混合型 I 型药物随机分组 AGYWLHIV 个体接受 LA 注射剂的有效性实施试验卡博特韦/利匹韦林与肯尼亚的护理标准的比较我们的核心前提是，使用 LA ART 将促进长期治疗。对健康的术语思考，包括预防怀孕，以及利用现有的洛杉矶避孕药具交付平台将使 LA ART 高度可行，目标 1a 将确定是否可以联合注射。卡博特韦/利匹韦林的使用与注射剂或植入剂有任何双向药物相互作用方法：通过重复血浆取样对卡博特韦/利匹韦林进行平行组 PK 评估。开始使用注射或植入式避孕药的使用者与未使用任何激素避孕药的使用者（总计 5 组，每组 n=21）。目标 1b 将定性探索趋同点和分歧点、偏好。和价值观，以及卫生系统对更广泛地共同提供 LA ART/避孕药具的准备情况：对来自上述前哨队列的 AGYW 进行 20-40 次系列、半结构化、深入访谈，以及 2-4 个焦点小组目标 2 将评估共同交付洛杉矶的影响。通过混合试验在 AGYWLHIV 中使用抗逆转录病毒治疗和避孕药具： (a) 艾滋病毒治疗的有效性结果（病毒抑制[主要结果]和依从性/持续性）和避孕（摄取和持续）率），以及（b）可接受性、可行性和保真度的实施结果方法：开放标签、临床-。提供混合方法混合试验，随机化 AGYW 1:1 切换至注射用卡博特韦/利匹韦林（干预组）与继续当前的口服 ART 治疗方案（对照组；总数 n=550）。