An Implementation Study of Long-acting Injectable Cabotegravir (CAB-LA) for HIV Pre-Exposure Prophylaxis (PrEP) Among Young MSM, Non-binary and Transgender Persons (The ImPrEP CAB Study)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,200
- 试验地点
- 1
- 主要终点
- Incident HIV infection
研究概览
简要总结
Although CAB LA PrEP has been proven efficacious in blinded randomized controlled clinical trials, additional research is needed to evaluate effectiveness in real world settings as well as to identify effective implementation strategies. The proposed implementation study will assess the safety and effectiveness of open label CAB LA PrEP when offered at public health facilities to cisgender men and transgender or gender non-binary individuals who have sex with persons assigned male at birth. The study will also evaluate two nested implementation strategies, an mHealth education and decision support tool and a WhatsApp injection appointment reminder. The study will also assess overall facilitators and barriers to integrating CAB LA into existing oral PrEP services.
详细描述
HIV Pre-Exposure Prophylaxis in Latin America: Results from randomized clinical trials and observational studies have proven that oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis (PrEP) is protective against HIV acquisition. This protection has been confirmed to be both effective and safe across all types of exposures, sexes and gender identities, and dosing regimens. PrEP is now recommended as part of the standard prevention regimen by the World Health Organization (WHO) for individuals at substantial risk of HIV infection. Increasing PrEP access is a priority in Latin America, where several countries have recorded a rising HIV infection incidence, particularly among men who have sex with men (MSM).
In 2020, there were an estimated 930,000 people in Brazil living with HIV (PLWH). Recent studies estimate an HIV prevalence among Brazilian MSM reaching approximately 23% and rates among transgender women (TGW) surpassing 30% in some cities. Young MSM are among the few populations with increasing numbers of new HIV infections in Brazil, where HIV incidence has stabilized in overall population. PrEP in Brazil is freely available through the national Public Health System. As of May 2022, there were 424 healthcare centers across all Brazilian states providing PrEP to approximately 343,000 individuals. Although over 80% of current PrEP users in Brazil are MSM, PrEP utilization remains well below the 2018 estimate of 66,120 Brazilian MSM aged 15-64 years who were eligible for and willing to use PrEP. This number is likely to be even higher with 2021 population estimates. Among more than 57,000 individuals that initiated PrEP in Brazil, approximately 43% discontinued its use. PrEP discontinuation was common among MSM (~40%) and TGW (over 50%).
Tenofovir-based oral PrEP has been effective in dramatically reducing population-level HIV incidence in multiple districts, including London, San Francisco, New South Wales, and in rural Kenya and Ugand. Despite these successes, PrEP has not decreased HIV incidence equally, particularly among the most at-risk populations (women, youth, racial and ethnic minority MSM, and TGW), due to user adherence challenges. PrEP Brasil, the Brazilian daily oral PrEP demonstration study, identified that 74% of overall participants had protective drug levels. Nevertheless, young participants and TGW had decreasing rates of protective drug concentrations throughout the study. In addition, data from the ImPrEP study, the largest PrEP demonstration study in Latin America with the goal of evaluating the feasibility of same-day PrEP implementation to MSM and transgender women in the context of the Public Health Systems of Brazil, Mexico, and Peru, identified lower PrEP adherence among transgender woman and individuals younger than 24 years of age.
To realize PrEP benefits, individuals need to both initiate PrEP and remain on PrEP during periods at-risk. In multiple studies, reasons for stopping or never initiating PrEP include, in addition to challenges accessing the medication, low self-perceived risk, concerns about medication side effects or a desire not to take a daily pill, stigma, or competing life events. Long-acting PrEP agents have the potential to address some of these concerns by providing consistent protection through infrequent, discrete administration, avoiding relying on adherence to a daily oral regimen and the need for disclosure with sex partners and acquaintances.
Long Acting Cabotegravir for Prevention: Long-acting injectable cabotegravir (CAB-LA) is a novel integrase strand-transfer inhibitor (INSTI). Two large randomized controlled trials (RCTs), known as HIV Prevention Trials Network (HPTN) Study 083 and HPTN Study 084, have demonstrated the effectiveness of injectable cabotegravir when compared to oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) PrEP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Cisgender men, non-binary (assigned as male at birth) or transgender women and men
- •Report having anal sex with a person assigned male at birth in the last six months (Persons born female having sex only with other persons born female are excluded)
- •Age 18-30 years
- •Seek a study clinic looking for PrEP
- •CAB LA and TDF/FTC PrEP naïve
- •Willing and able to provide written informed consent and adhere to the study requirements
- •Non-reactive / negative HIV test results, including both HIV rapid tests and an undetectable HIV RNA at enrollment for individuals choosing injectable CAB-LA.
- •No report of hepatic dysfunction. Candidates reporting liver disease will have their enrollment visit postponed until laboratory results of liver function are available. Individuals with ALT >=5x ULN, OR ALT>=3xULN and bilirubin >=1.5xULN will be excluded. See section 7 (Study Procedures - Enrollment visit).
- •Willing to undergo all required study procedures.
排除标准
- •One or more reactive or positive HIV test result at enrollment visit, even if HIV infection is not confirmed.
- •Currently participating in interventional trial of PrEP agents, HIV vaccine trial or experimental medication.
- •Positive pregnancy test, breastfeeding, or intention to become pregnant at enrolment (for transgender men).
- •Prior participation in studies with Cabotegravir.
- •A history or presence of allergy to the study drug components.
- •Past participation in HIV vaccine trial. An exception will be made for participants that can provide documentation of receipt of placebo (not active arm).
- •Plan to relocate out of the area during the study period.
- •Surgically placed or injected buttock implants or fillers, per self-report.
- •Has a dermatological/inflammatory skin condition overlying the buttock region which in the opinion of the study investigator, in consultation with the Clinical Study Coordination (CSC), may interfere with interpretation of injection site reactions.
- •Active or planned use of contraindicated co-administered for which significant decreases in Cabotegravir plasma concentrations may occur due uridine diphosphate glucuronosyltransferase (UGT1A1):
- •Anticonvulsants: Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin
- •Antimycobacterials: Rifampin, Rifapentine *Any prohibited medications that decrease CAB concentrations should be discontinued for a minimum of four weeks or a minimum of three half-lives (whichever is longer) prior to the first dose.
- •Current or anticipated need for chronic systemic anticoagulation or a history of known or suspected bleeding disorder, including a history of prolonged bleeding.
- •History of severe hepatic impairment (including but not limited to a history of liver failure or hospitalization for liver disease, a history of hepatocellular carcinoma or near liver transplant).
- •Individuals with advanced Hepatitis C.
- •Other medical conditions that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical).
研究组 & 干预措施
Injectable Cabitegravir
Participants that are interested in Cab long action injectable
干预措施: Cabotegravir Injection (Drug)
结局指标
主要结局
Incident HIV infection
时间窗: 2 years
Among individuals who test positive on HIV rapid test, midpoint between last negative HIV rapid test and first HIV positive rapid test
次要结局
未报告次要终点
研究者
Raquel Malaguthi de Souza
Beatriz Grinsztejn, MD, PhD
Evandro Chagas National Institute of Infectious Disease