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).

项目摘要抗逆转录病毒疗法（ART）的第一个完整的长效（LA）公式，可注射的Cabotegravir Rilpivirine是临床批准的风口浪尖 - 这是艾滋病毒改变游戏规则的发展治疗领域。 LA艺术方案增加了患者和提供者改善患者依从性和持续治疗。几个亚群，包括青春期的女孩和年轻女性（AGYW，年龄） 15-24），落后于第三90-90-90个统一的病毒抑制目标，包括在肯尼亚。 Agyw与艾滋病毒一起生活（Agywlhiv）在持久性艺术方面面临独特的挑战，洛杉矶艺术选择有可能提供帮助与口腔艺术相比，通过更大的信心和污名化来克服其中一些挑战。对AGYW健康的另一个主要威胁是意想不到的怀孕，Agywlhiv也面临独特 LA避孕药的吸收和延续率的挑战。最近，使用LA避孕药，其中包括可注射和可植入的方法，在肯尼亚获得了明显的动量，许多艾滋病毒治疗计划已将避孕药提供为常规的艾滋病毒护理，包括agwy。此外，Agywlhiv对艺术和避孕药的共同交付非常感兴趣。但是，共同交付还提出了需要进一步研究的药物和行为的潜在问题。我们提出了基础药代动力学（PK）和定性研究，导致I型混合动力学有效性实施试验随机将个体agywlhiv随机接收LA注射 Cabotegravir/Rilpivirine vs.肯尼亚的护理标准。我们的中心前提是，洛杉矶艺术的使用将长期培养对健康的期限，包括预防怀孕，并利用现有的LA避孕药交付平台将使洛杉矶艺术高度可行。 AIM 1A将确定是否合并注射 Cabotegravir/rilpivirine使用与可注射或可植入的双向药物相互作用避孕药。方法：平行组PK评估，在cabotegravir/rilpivirine之间进行重复等离子采样用户启动可注射或可植入的避孕药与不使用任何激素避孕药的避孕药（总计5 组，每组n = 21）。 AIM 1B将定性地探索融合和差异点，偏好和价值，以及围绕洛杉矶艺术/避孕药的大规模共同交付的卫生系统准备就绪。方法： 20-40串行，半结构化的，深入的访谈与AGYW上面的哨兵队列和2-4焦点小组与提供者，政策制定者和利益相关者的讨论。 AIM 2将评估LA共同交付的影响 Agywlhiv中的艺术和避孕药通过混合试验：（a）HIV治疗的有效性结果（病毒抑制[主要结果]和依从性/持久性）和避孕（吸收和延续费率），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，诊所 - 提供的混合方法混合试验，随机化AGYW 1：1切换到可注射的Cabotegravir/rilpivirine （干预臂）与继续进行目前的口腔艺术方案（控制臂；总n = 550）。