Clinical Opportunities and Management to Exploit Biktarvy as Asynchronous Connection Key (COMEBACK)

Study Overview
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Brief Summary
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COMEBACK is an investigator-initiated, 48-week study. The study will be conducted in 100 persons living with HIV (PLWH) who have been off ART for two or more weeks. All enrolled participants will be prescribed Biktarvy, if determined appropriate upon review of past historical resistance tests, for use throughout the study period. Participants will also complete a series of Patient Reported Outcomes (PROs) at screening and be assigned one of three tiers of case management intervention (Piggyback, Got Your Back, Backbone), with each tier increasing in intensity regarding intervention techniques and options provided. Participants will be assessed for virologic suppression, retention in care, and PROS throughout study follow up and at study end.

Detailed Description
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In most settings in the US when patients out of care and off of ART reengage with clinical providers routine labs are collected, including CMP, CD4, VL, and HIV resistance testing when indicated, healthcare benefits are reassessed, and the most recent ART regimen is restarted if the patient agrees to treatment. There may be characteristics of these regimens that may present barriers to sufficient adherence, or perform suboptimally in patients with certain immunologic and/or viral factors, which may impact virologic suppression, including multiple pills, drug-drug interactions, variable tolerability, low CD4, high VL, or low thresholds for resistance. Biktarvy is a Single Tablet Regimen (STR) with high potency and good tolerability that can be safely used in multiple patient groups, with features, including activity in patients with a history of multi-class resistance, that may facilitate immediate ART reinitiation among a broad population of patients reengaging in care in order to promote rapid virologic suppression. Addressing this important patient population with poor retention with support mechanisms to reengage in care and reinitiate effective ART immediately may improve retention in care and accelerate virologic suppression as likewise derived in immediate ART models in treatment-naïve patients, and represent a touchstone to drive sustainability in preventing new HIV transmissions in a high burden area to meet the goals of reducing HIV as a public health threat over the next 10 years.

Official Title
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(COMEBACK): Biktarvy in PLWH But Not Retained in Care Coupled With a Strengths-based Case Management Approach to Assess Virologic Suppression Rates and Retention in Care, Along With Patient Reported Outcomes (PROS).

Conditions
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Hiv

Intervention / Treatment
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* Behavioral: Case Management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-infected Not on ART for >2 weeks History of estimated eGFR > 30 ml3/min Baseline labs (CBC, CMP, CD4+, HIV-1 RNA) and resistance genotype test collected <2 weeks or on day of Biktarvy ART reinitiation 18 years or older Exclusion Criteria: No history of primary integrase inhibitor mutations, >3 TAMs, K70E, Q151M, T69 insertion, or K65R + M184V/I on prior resistance testing Drug-drug interactions with Biktarvy Pregnancy Unable or unwilling to provide consent for study participation Any condition that, in the opinion of the Investigator of Record (IoR), would make participation in the study unsafe, complicate interpretation of outcome data, or otherwise interfere with achieving the study objective. Current participation in another ART adherence study Allergy to bictegravir, emtricitabine or tenofovir alafenamide Signs or symptoms of opportunistic infection with cryptococcal meningitis, tuberculosis or other infection that requires delay of reinitiation of antiretroviral therapy Concomitant use of medications that are contraindicated with bictegravir, emtricitabine and tenofovir alafenamide including adefovir, carbamazepine, cladribine, dofetilide, fosphenytoin-phenytoin, oxcarbazepine, phenobarbital, primidone, rifampin, rifabutin, rifapentine, St. John's Wort, tipranavir

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Highest Tier of Case Management (Piggyback) and Biktarvy<br>The most intensive tier of case management. Includes three appointment reminders; check ins twice per week; travel compensation; housing support; food insecurity support; follow ups for missed appointments and off pill counts; connections with substance use programs; meetings with the benefits department for health insurance needs; childcare support to make appointments; mental healthcare referrals; open pool appointments as back-up options in case of rescheduling needs; late doctor's appointments and prescription pick up for those working during the day; meetings with the health educators to discuss HIV and ART; and re-motivation of HIV treatment every 3 months. | Behavioral: Case Management<br>* Each tier will have a different level of case management and support, all with the goal of increasing adherence to Biktarvy for HIV management.<br>|
| Active Comparator: Middle Tier of Case Management (Got Your Back) and Biktarvy<br>The middle tier (Got Your Back) will work closely with the CORE case managers to augment their work in housing support, transportation assistance, mental healthcare referrals, childcare assistance, substance use program referrals, food insecurity support and health insurance needs. The retention specialist will additionally provide this middle tier 2 reminders for appointments; check ins once per week; follow ups for missed appointments or off pill counts; support with scheduling appointments for limited availability; meetings with the health educators for information on HIV or ART; and re-motivation for treatment at the 6 and 9 month marks of participation. | Behavioral: Case Management<br>* Each tier will have a different level of case management and support, all with the goal of increasing adherence to Biktarvy for HIV management.<br>|
| Active Comparator: Lowest Tier of Case Management (Backbone) and Biktarvy<br>The top tier (Backbone) will need the least amount of support and also have a CORE Center case manager for a majority of the support in housing, food, insurance, transportation, childcare, substance use, and mental healthcare. The retention specialist will still provide an appointment reminder; check ins every other week; text checkups after missed appointments or off pill counts; support with scheduling for appointments or prescription pick up for limited availability; and re-motivation of treatment for HIV at the 9 month mark of study participation. | Behavioral: Case Management<br>* Each tier will have a different level of case management and support, all with the goal of increasing adherence to Biktarvy for HIV management.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic Suppression Rates | Number of patients with virologic suppression, defined as HIV RNA <50 copies/ml at week 24 RNA. | 1 year | 
| Retention in Care | Number of patients retained in study, defined as at least 2 visits or 2 HIV-1 RNA viral load reports occurring at least 3 months apart within the 12-month study time period | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Reported Outcomes concerning social and health related barriers | Favorable outcomes concerning health and and social related determinants as assessed by responses to a series of Patient Reported Outcomes at 6 and 12 months. See full list in attached documents. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adherence, Case Management, Biktarvy