Extension of SEARCH SAPPHIRE Dynamic Choice Prevention Study

Study Overview
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Brief Summary
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The overall purpose of this SEARCH SAPPHIRE CAB-LA (Cabotegravir Injectable Suspension) extension study is to 1) Determine if adding the option of CAB-LA as a prevention choice using a patient-centered HIV (human immunodeficiency virus) prevention delivery model increases prevention coverage compared to the standard-of-care in three ongoing randomized trials of Dynamic Choice Prevention in rural Uganda and Kenya; and, 2) Conduct a hybrid implementation study (Primary Objective Clinical and Secondary Objective Implementation) focusing on initial implementation of a patient-centered model for CAB-LA using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) evaluation framework among persons randomized to the intervention arms.

Detailed Description
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The SEARCH SAPPHIRE CAB-LA (Cabotegravir Injectable Suspension) extension study a 48 week extension of three ongoing randomized trials studying a patient-centered Dynamic Choice Prevention (DCP) implementation strategy for delivering existing evidence-based biomedical prevention interventions vs. standard of care (SOC). The Dynamic prevention model offers participants choices on prevention modality on an ongoing basis: oral Pre-Exposure Prophylaxis (PrEP), or oral post-exposure prophylaxis (PEP), and the option to switch between products. The trials are being conducted in 3 settings: antenatal (ANC) clinics, the outpatient department (primary care clinics), and in rural community settings in Western Kenya and Uganda. All clinic and village health team staff (i.e., Clinical Officers, nurses, coordinators, health workers) are trained and equipped for HIV prevention care in the clinical setting, appropriate to their role. In the CAB-LA extension, participants in the intervention and control arms are reconsented and remain in their initial randomized arm. Persons in the intervention arms who remain HIV negative will be offered CAB-LA as an additional biomedical prevention option, if eligible. CAB-LA will be delivered at health clinics. The primary 48 week endpoint for this extension is proportion of time covered by a biomedical prevention product.

Official Title
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A Multisectoral Strategy to Address Persistent Drivers of the HIV Epidemic in East Africa: Extension of SEARCH SAPPHIRE Dynamic Choice Prevention Study

Conditions
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HIV

Intervention / Treatment
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* Drug: Cabotegravir Injectable Suspension
* Other: Dynamic Choice Delivery Model
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for the Extension include: Enrollment in a SEARCH Sapphire Dynamic prevention study (NCT04810650) HIV negative at start of extension Residing in study region Additional inclusion criteria to access CAB-LA as a prevention option Not pregnant or breastfeeding at time of initial CAB-LA injection Participant weighs at least 35kg Exclusion Criteria: Exclusion criteria to access CAB-LA as a prevention option: Participant has Hepatitis B or chronic Hepatitis C Diagnosis Participant has ALT >=5x ULN Participant has clinical history of liver cirrhosis or current clinical evidence of cirrhosis Previous hypersensitivity reaction to cabotegravir Receiving the following co-administered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase: i. Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin ii. Antimycobacterials: Rifampin, rifapentine Participants with a current or anticipated need for chronic systemic anticoagulation or a history of known or suspected bleeding disorder, including a history of prolonged bleeding, except for the use of anticoagulation for deep vein thrombosis (DVT) prophylaxis (e.g., postoperative DVT prophylaxis) or the use of low dose acetylsalicylic acid (≤325 mg).

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants initially randomized to the Dynamic Choice Prevention delivery model will be given the option to use CAB-LA as part of the dynamic choice prevention delivery package. Participants initially randomized to standard of care will continue to receive standard of care.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dynamic choice prevention (including CAB LA)<br>The Dynamic Choice Delivery Model includes integrated PrEP and PEP services at outpatient clinics, antenatal clinics, and via VHT workers in community households. CAB-LA will be integrated into the dynamic choice delivery model as an additional biomedical prevention option in a patient-centered delivery model based on the precede framework. | Drug: Cabotegravir Injectable Suspension<br>* CAB-LA will be one of the options for the Dynamic Choice Delivery intervention arm. CAB-LA will be a choice for at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Single-dose vial containing 600 mg/3 mL (200 mg/mL) of cabotegravir is a white to light pink, free-flowing, extended-release injectable suspension. CAB-LA administration will occur at health facilities.<br>Other: Dynamic Choice Delivery Model<br>* The Dynamic Choice Delivery Model includes integrated PrEP (including CAB-LA) and PEP services at outpatient clinics, antenatal clinics, and via VHT workers in community households. The procedures for each trial include PrEP/PEP counseling and services, choice of service location, HIV testing options, option for longer PrEP refills, provision of a clinical officer's or nurse's mobile telephone number for immediate PEP starts any day of the week, assessment of PrEP/PEP barriers and personalized actions, psychologic supports for traumatic experiences, and offer of concurrent, additional health or prevention related services.<br>|
| Active Comparator: Standard of Care<br>The standard of care for PEP or PrEP differs according to each country's guidelines. | Other: Standard of Care<br>* The standard of care differs according to country but does not routinely offer PEP or PrEP to clients seeking services, does not offer choice of service location, HIV testing option or access to medical provider mobile phone number.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomedical prevention covered time | Number of weeks participant taking biomedical prevention divided by number of weeks participant biomedical prevention use measured. Biomedical prevention includes PrEP tenoofovir disoproxil fumarate/lamivudine (TDF/3TC) or cabotegravir long-acting injectable (CAB-LA) and PEP | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cabotegravir Injectable Suspension, PrEP, HIV Treatment and Prevention, Community Health, Youth and Adolescents