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

项目摘要 抗逆转录病毒治疗（ART）的第一个完整的长效（LA）制剂，可注射的cabotegravir 和利匹韦林，正处于临床批准的风口浪尖-这是一个潜在的改变游戏规则的发展，在艾滋病毒 治疗领域LA ART方案增加了患者和提供者的选择，以提高患者的依从性， 坚持治疗。包括少女和年轻妇女在内的几个亚群（AGYW，年龄 15 - 24），落后于艾滋病规划署的第三个90 - 90 - 90病毒抑制目标，包括在肯尼亚。艾滋病毒感染者 （AGYWLHIV）在坚持ART方面面临独特的挑战，LA ART选择有可能帮助 与口服抗逆转录病毒药物相比，通过更高的保密性和减少耻辱感来克服其中一些挑战。 对AGYW健康的另一个主要威胁是意外怀孕，AGYWLHIV也面临着独特的风险。 LA避孕药具的使用率和持续率方面的挑战。最近，LA避孕药的使用， 包括注射和植入方法，在肯尼亚获得了显著的势头， 治疗方案已将避孕措施纳入常规艾滋病毒护理，包括AGWY。 此外，AGYWLHIV对同时提供抗逆转录病毒疗法和避孕药具非常感兴趣。然而，共同交付 也提出了潜在的问题，药理学和行为学，需要进一步调查。 我们提出基础药代动力学（PK）和定性研究，导致混合I型 有效性实施试验随机分配AGYWLHIV个体接受LA注射剂 cabotegravir/rilpivirine vs肯尼亚标准治疗。我们的核心前提是，使用LA ART将促进长期- 长期的健康思考，包括预防怀孕，以及利用现有的LA避孕药 交付平台将使LA ART高度可行。目标1a将确定是否联合注射 卡替拉韦/利匹韦林的使用与可注射或可植入药物之间存在任何双向药物相互作用 避孕药方法：卡替拉韦/利匹韦林之间重复血浆采样的平行组PK评价 开始使用注射或植入避孕药的使用者与未使用任何激素避孕药的使用者（共5 每组n = 21）。目标1b将定性地探讨趋同点和分歧点、偏好 和价值观，以及卫生系统围绕大规模共同提供LA ART/避孕药具的准备情况。方法： 对来自上述哨兵队列的AGYW进行20 - 40次系列、半结构化、深入访谈，以及2 - 4次焦点小组访谈 与供应商、政策制定者和利益攸关方进行讨论。目标2将评价LA联合给药的影响 通过一项关于以下问题的混合试验在AGYWLHIV人群中使用抗逆转录病毒疗法和避孕药具：（a）艾滋病毒治疗的有效性结果 （病毒抑制[主要结局]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- 提供了混合方法混合试验，将AGYW 1：1随机转换为注射用卡替拉韦/利匹韦林 （干预组）与继续其当前口服ART方案（对照组;总计n = 550）。

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).