REINItiation of Antiretroviral Therapy Using Oral bicTegravir, emtrIcitAbine and Tenofovir alafenamidE (REINITIATE)

A Multi-Center, Single-Arm, Open-Label, Prospective, Phase 4 Study to Investigate the Safety and Efficacy of Rapidly Restarting Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide (B/F/TAF) in Viremic and Virologically-Suppressed Male and Female HIV-Positive Patients Aged ≥18 Years Who Are Treatment-Experienced and Returning to Care After Experiencing a Treatment Interruption of ≥12 Weeks

Managing HIV well requires taking antiretroviral therapy (ART) every day, but many people living with HIV experience interruptions in their treatment. These pauses in medication can happen for many reasons, such as side effects, challenges with getting to the clinic, personal circumstances, stigma, or difficulties with everyday life. When HIV treatment is stopped, the viral load can increase, which may affect a person's health and make it easier for HIV to be passed on to others. Restarting treatment quickly after an interruption is important for both personal and public health. However, it can be difficult for people who miss doses to get back on treatment right away. There are often several steps and medical appointments required before restarting, such as waiting for lab results or reviewing medical history, which can cause further delays. These additional steps can make it even harder for people to re-engage and may discourage them from returning to care.

The REINITIATE study is designed for people living with HIV who have not taken any antiretroviral medications for at least the last 12 weeks. The study will offer participants a way to restart their HIV therapy quickly, by beginning treatment with B/F/TAF on the same day that they return to care. B/F/TAF is a widely used, once-daily HIV regimen, and is recommended in national treatment guidelines.

Researchers want to find out if this rapid restart approach is safe and effective, and whether it helps people regain control of HIV and remain in care. The study will also examine how many participants are able to keep the virus at a low level (viral suppression), stay engaged in their HIV care, and tolerate the medication after rapidly restarting treatment. In addition, the study will include interviews with some participants, to gain a better understanding of why they stopped taking their medications and what supported their return to treatment. These insights could help healthcare teams develop better ways to support people living with HIV in the future.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV; HIV 1 Infection; HIV -1 Infection; HIV (Human Immunodeficiency Virus)
• Intervention / Treatment: Drug: Bictegravir, emtricitabine, and tenofovir alafenamide

Detailed Description

This prospective, multicenter, open-label, single-arm, Phase 4, interventional study aims to evaluate rapid antiretroviral therapy (ART) restart with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in participants' routine clinical environments, facilitating data collection on treatment effectiveness and safety following same-day ART reinitiation amongst treatment-experienced people with HIV (PWH) who have had a treatment interruption of at least 12 weeks. This study will also characterize reasons for ART interruption and reinitiation.

B/F/TAF, a three-drug combination of bictegravir (B; a second-generation HIV-1 integrase strand transfer inhibitor [INSTI]), and emtricitabine (F) and tenofovir alafenamide (TAF), both nucleoside reverse transcriptase inhibitors (NRTIs), is a recommended initial ART regimen for most people with HIV in the United States. B/F/TAF is an oral, once-daily fixed-dose combination (FDC) that provides a potent and well-tolerated regimen for the treatment of HIV-1 infection in people, including those with some pre-existing resistance and subpopulations that are underrepresented in clinical trials, including Black, Hispanic, and Latine PWH, PWH ≥65 years old, and pregnant adults.

The rapid restart nature of this study involves the concurrent initiation of screening, baseline assessments, and administration of B/F/TAF on the same day. B/F/TAF is the only guideline-recommended single tablet regimen (STR) suitable for rapid restart, as it can be prescribed without prior knowledge of baseline laboratory parameters, including viral load, hepatitis B virus (HBV) status, or baseline genotypic resistance testing. This means the study treatment commences without baseline test results, provided the participant fulfills all eligibility criteria.

There will be two Cohorts of participants within this study: Cohort 1 will include viremic participants (defined by HIV-1 RNA ≥50 copies/mL) at baseline and Cohort 2 will include virologically suppressed participants (defined by HIV-1 RNA <50 copies/mL) at baseline. The study will aim to recruit 125 participants into Cohort 1 while simultaneously recruiting into Cohort 2 (it is assumed approx. 15-75 participants). The ratio of participants in Cohort 1 and Cohort 2 will be monitored during enrollment. Adherence and drop-out rates will be closely monitored throughout the study to mitigate the risk of insufficient sample sizes to power the planned analyses. Each participant's total study participation duration will be up to 48 weeks for data collection. Participants will be followed prospectively for 48 weeks in Cohort 1 and for 24 weeks in Cohort 2. Optional, semi-structured interviews will be conducted for a subset of participants in Cohorts 1 and 2 via teleconference at week 4 and week 24 after baseline screening and treatment reinitiation. While sample size will be informed by theoretical saturation, ~30 participants (15 per Cohort) is estimated to be sufficient.

Achieving viral suppression (defined as HIV-1 RNA <50 copies/mL) is the main goal of ART therapy for PWH who are viremic, and the primary objective of this study. It has been associated with improvements in CD4 cell counts, prevention of HIV drug resistance, AIDS- and non-AIDS-related events, and decreased transmission to sexual partners of PWH. Secondary outcomes include safety, resistance, persistence and adherence, and a range of patient-reported outcomes to understand patient experiences of ART.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Prerak Shukla, MD; Phone Number: 11102 941-366-0134; Email: pshukla@cancommunityhealth.org
• Study Contact Backup: Name: Miranda Townsend; Phone Number: +44 7709-514-696; Email: biktarvy.rapidrestartstudy@costellomedical.com

Study Locations

• United States
  • Florida
    • Clearwater, Florida, United States, 33765
      • CAN Community Health
      • Contact: Jessica Altamirano, MD; Phone Number: 786-800-5631; Email: jaltamirano@cancommunityhealth.org
      • Contact: Jeanette Cancel, MD; Phone Number: 727-216-6193; Email: jcancel@cancommunityhealth.org
      • Sub-Investigator: Jeanette Cancel, MD
    • Ft. Pierce, Florida, United States, 34982
      • Midway Specialty Care Center
      • Contact: Hector Bolivar, MD; Phone Number: 561-249-2279; Email: drbolivar@midwaycare.org
      • Contact: Jenn L Kuretski, DNP, APRN, NP-C,AAHIVS; Phone Number: 772-464-9746; Email: Jkuretski@midwaycare.org
      • Sub-Investigator: Moti Ramgopal, MD
      • Sub-Investigator: Angela Trodglen, APRN
    • Jacksonville, Florida, United States, 32207
      • CAN Community Health
      • Contact: Jessica Altamirano, MD; Phone Number: 786-800-5631; Email: jaltamirano@cancommunityhealth.org
      • Contact: Katherine Rogers, APRN; Phone Number: 904-508-0701; Email: krogers@cancommunityhealth.org
      • Sub-Investigator: Katherine Rogers, APRN
    • Orlando, Florida, United States, 32819
      • Midway Specialty Care Center
      • Contact: Hector Bolivar, MD; Phone Number: 561-249-2279; Email: drbolivar@midwaycare.org
      • Contact: Jenn L Kuretski, DNP, APRN, NP-C, AAHIVS; Phone Number: 407-745-1171; Email: Jkuretski@midwaycare.org
      • Sub-Investigator: Emmanuelle Allseits, MD
      • Sub-Investigator: Aylin Perez, PA
    • Orlando, Florida, United States, 32804
      • CAN Community Health
      • Contact: Jessica Altamirano, MD; Phone Number: 786-800-5631; Email: jaltamirano@cancommunityhealth.org
      • Contact: Vincenzo Scotto D'Antuono, MD; Phone Number: 407-246-1946; Email: vsdantuono@cancommunityhealth.org
      • Sub-Investigator: Vincenzo Scotto D'Antuono, MD
    • Tampa, Florida, United States, 33602
      • CAN Community Health
      • Contact: Jessica Altamirano, MD; Phone Number: 786-800-5631; Email: jaltamirano@cancommunityhealth.org
      • Contact: Elier Rodriguez, MD; Phone Number: 941-300-4440; Email: erodriguez@cancommunityhealth.org
      • Sub-Investigator: Elier Rodriguez, MD
    • Temple Terrace, Florida, United States, 33617
      • Midway Specialty Care Center
      • Contact: Hector Hector, MD; Phone Number: 561-249-2279; Email: drbolivar@midwaycare.org
      • Contact: Jenn L Kuretski, DNP, APRN, NP-C, AAHIVS; Phone Number: 813-733-8224; Email: Jkuretski@midwaycare.org
      • Sub-Investigator: Rodrigo Sabec, APRN
    • West Palm Beach, Florida, United States, 33409
      • Midway Specialty Care Center
      • Contact: Hector Bolivar, MD; Phone Number: 561-249-2279; Email: drbolivar@midwaycare.org
      • Contact: Jenn L Kuretski, DNP, APRN, NP-C, AAHIVS; Phone Number: 561-249-2279; Email: Jkuretski@midwaycare.org
      • Sub-Investigator: Jenn L Kuretski, DNP, APRN, NP-C, AAHIVS
    • Wilton Manors, Florida, United States, 33334
      • Midway Specialty Care Center
      • Contact: Hector Bolivar, MD; Phone Number: 561-249-2279; Email: drbolivar@midwaycare.org
      • Contact: Jenn L Kuretski, DNP, APRN, NP-C, AAHIVS; Phone Number: 954-530-8357; Email: Jkuretski@midwaycare.org
      • Sub-Investigator: Isabel Gomez, MD
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • CAN Community Health
      • Contact: Jessica Altamirano, MD; Phone Number: 786-800-5631; Email: jaltamirano@cancommunityhealth.org
      • Contact: Archer Grimley, MD; Phone Number: 702-979-1111; Email: archgrimley@cancommunityhealth.org
      • Sub-Investigator: Archer Grimley, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years of age at the time of signing the informed consent form (ICF)
• Diagnosis of HIV-1 confirmed by any positive HIV 4th generation test or detectable HIV-1 RNA level in >6 months
• Previously received ART for ≥30 consecutive days, as self-reported
• No ART dose received for ≥12 weeks prior to provision of informed consent, by any route of administration (i.e., injection or oral), as self-reported
• Returning to care with an interest to restart ART therapy
• Body weight ≥25 kg
• Signed ICF which includes compliance with the requirements and restrictions listed in ICF and study protocol

Exclusion Criteria:

• Diagnosis of HIV-2 infection
• Known or suspected history of severe hepatic impairment (Child-Pugh Class C)
• Known or suspected history of severe renal impairment (estimated creatinine clearance [eCrCl] <30 mL/min)
• Concomitant medication that is contraindicated with B/F/TAF
• Known or suspected resistance to BIC (resistance-associated mutations (RAMs) include: T66A/I/K, E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene)
• Known/suspected resistance to TFV (RAMs include: K65R/E/N, or K70E)
• Known/suspected history of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT
• History of B/F/TAF intolerance
• Unable to swallow whole tablets or swallow tablets cut into halves
• Unable to communicate in either English or Spanish

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-label B/F/TAF; All participants receive open-label B/F/TAF. Treatment duration is determined by baseline viral load: viremic participants (defined by HIV-1 RNA ≥50 copies/mL) at baseline will receive 48 weeks of B/F/TAF; virologically suppressed participants (defined by HIV-1 RNA <50 copies/mL) at baseline will receive 24 weeks of B/F/TAF.	Drug: Bictegravir, emtricitabine, and tenofovir alafenamide; Oral, film-coated tablet containing 50 mg BIC, 200 mg FTC, and 25 mg TAF taken once daily with or without food administered for 24 or 48 weeks.; Other Names: BIKTARVY®; B/F/TAF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants in Cohort 1 with plasma HIV-1 RNA <50 copies/mL	Percentage of all participants who have plasma HIV-1 RNA Viral Load <50 c/mL at W24 using FDA snapshot analysis, which defines a participant's virologic response status using only the viral load at the predefined timepoint within a certain window of time, along with study drug discontinuation	Week 24
Percentage of participants in Cohort 2 with plasma HIV-1 RNA ≥50 copies/mL	Percentage of all participants who have plasma HIV-1 RNA Viral Load ≥50 c/mL at W24 using FDA snapshot analysis, which defines a participant's virologic response status using only the viral load at the predefined timepoint within a certain window of time, along with study drug discontinuation	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with plasma HIV-1 RNA <50 copies/mL	Percentage of participants with HIV-1 RNA <50 copies/mL assessed at Weeks 12, 24, and 48, using FDA snapshot analysis and missing values excluded	48 weeks
Percentage of participants with plasma HIV-1 RNA <200 copies/mL	Percentage of participants with HIV-1 RNA <200 copies/mL assessed at Weeks 12, 24, and 48, using FDA snapshot analysis and missing values excluded	48 weeks
Percentage of participants meeting protocol-defined virologic failure (PDVF) criteria in Cohort 1	Percentage of participants meeting PDVF criteria through Weeks 24 and 48. For Cohort 1, PDVF will be defined as Suboptimal Virologic Response, in which HIV-1 RNA ≥50 copies/mL and less than 1 log10 HIV-1 RNA reduction from Day 1 at the W12 visit, or Virologic Rebound, in which at any timepoint after achieving HIV-1 RNA <50 copies/mL, a subsequent HIV-1 RNA measurement is noted to be ≥50 copies/mL, which is then confirmed at the following scheduled or unscheduled visit	48 weeks
Percentage of participants meeting PDVF criteria in Cohort 2	Percentage of participants meeting PDVF criteria through Weeks 24 and 48. For Cohort 2, PDVF will be defined as Confirmed Virologic Rebound, in which at any visit after Day 1, a rebound in HIV-1 RNA to ≥50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled visit, or any participant with HIV-1 RNA ≥50 copies/mL at the last on-treatment study visit (including E/D, lost to follow-up, or study endpoints)	24 weeks
Absolute and change from baseline in log10 HIV-1 RNA viral load of participants	Absolute and change from baseline in log10 HIV-1 RNA viral load at Weeks 12, 24, and 48	48 weeks
Absolute and change from baseline CD4 T-cell count of participants	Absolute and change from baseline CD4 T-cell count at Weeks 12, 24, and 48. The CD4 T-cell count will be determined using the participant's blood sample. This test serves as a marker of immune system integrity and is used to evaluate immune suppression and disease progression, and monitor B/F/TAF efficacy	48 weeks
Percentage of participants discontinuing due to adverse events (AEs) or intolerability	Percentage of patients discontinuing study treatment due to AEs or other intolerability through Weeks 24 and 48	48 weeks
Percentage of participants experiencing treatment-emergent Grade 3-4 laboratory abnormalities	Incidence of new Grade 3-4 lab abnormalities through Weeks 24 and 48	48 weeks
Percentage of participants experiencing treatment-emergent Grade 3-4 drug-related adverse events	Incidence of Grade 3-4 adverse events considered drug-related through Weeks 24 and 48	48 weeks
Percentage of Participants experiencing Serious Adverse Events (SAEs)	Incidence of SAEs through Weeks 24 and 48. All SAEs will be collected from the date of the first dose of the study drug until the end of on-study treatment + 30 days	48 weeks
Baseline resistance to B/F/TAF	Proportion of participants with pre-existing genotypic or phenotypic resistance to any component of B/F/TAF at study entry	4 weeks
Treatment-emergent resistance in PDVF participants in Cohort 1	Proportion of participants with PDVF who develop treatment-emergent genotypic or phenotypic resistance to any component of B/F/TAF. For Cohort 1, PDVF will be defined as Suboptimal Virologic Response, in which HIV-1 RNA ≥50 copies/mL and less than 1 log10 HIV-1 RNA reduction from Day 1 at the W12 visit, or Virologic Rebound, in which at any timepoint after achieving HIV-1 RNA <50 copies/mL, a subsequent HIV-1 RNA measurement is noted to be ≥50 copies/mL, which is then confirmed at the following scheduled or unscheduled visit	48 weeks
Treatment-emergent resistance in PDVF participants in Cohort 2	Proportion of participants with PDVF who develop treatment-emergent genotypic or phenotypic resistance to any component of B/F/TAF. For Cohort 2, PDVF will be defined as Confirmed Virologic Rebound, in which at any visit after Day 1, a rebound in HIV-1 RNA to ≥50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled visit, or any participant with HIV-1 RNA ≥50 copies/mL at the last on-treatment study visit (including E/D, lost to follow-up, or study endpoints)	24 weeks
Reasons for prior ART discontinuation and current reinitiation	Participant-reported reasons for previous ART discontinuation and for reinitiation at study entry	Baseline
Proportion of participants lost to follow-up	Participants with no study contact through Week 48	Week 48
Proportion of participants on study drug with documented clinic visit	Participants taking study drug at Week 48 who have a clinic visit within 90 days after their post-treatment safety follow-up visit (Week 48 + 30 days)	Week 48
Adherence to B/F/TAF by pill count or dried blood spot (DBS)	Adherence rate as measured by pill counts or DBS at scheduled and/or unscheduled visits through Week 48	Week 48
Participant experiences returning to care after HIV treatment interruption	Semi-structured qualitative interviews will be conducted at Weeks 4 and 24 to investigate the experience of PWH who are returning to care after interrupting treatment, including barriers to initial retention in care and reasons for disengagement, motivators for re-engagement with care, as well as barriers to this process, perceptions about future risk of disengagement with care following re-engagement, and impact of restarting treatment on first visit with B/F/TAF	Week 24
Total satisfaction score on the HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs)	Total score at Weeks 4, 24, and 48 on the HIVTSQs on a scale of 0 (very dissatisfied) to 6 (very satisfied)	48 weeks
Change from Week 4 on the Total HIV Treatment Satisfaction Questionnaire - Status Version (HIVTSQs) score	Change in total HIVTSQ satisfaction score from Week 4 to Weeks 24 and 48 on a scale of 0 (very dissatisfied) to 6 (very satisfied)	48 weeks
Total and change from baseline in the symptom distress score on the HIV-Symptom Index (HIV-SI)	Total score and change from baseline at Weeks 4, 24, and 48 on the HIV-SI on a scale of 0 ("I do not have this symptom") to 4 ("It bothers me a lot")	48 weeks
Health-related quality of life by EuroQol 5-Dimension 5-Level (EQ-5D-5L) total score and change from baseline	Total EQ-5D-5L score and change from baseline at Weeks 4, 24, and 48 with a scale ranging from 0 (the worst health you can imagine) to 100 (the best health you can imagine)	Week 4

Collaborators and Investigators

• Sponsor: CAN Community Health
• Collaborators: Gilead Sciences; Midway Specialty Care Center; Costello Medical Inc.
• Investigators: Principal Investigator: Jessica Altamirano, MD, CAN Community Health; Principal Investigator: Hector Bolivar, MD, Midway Specialty Care Center

Publications and helpful links

General Publications

• Peters E, Iwuji AC. Efficacy, safety and tolerability of Biktarvy in HIV-1 infection: A scoping review. Antivir Ther. 2023 Feb;28(1):13596535231159030. doi: 10.1177/13596535231159030.

Helpful Links

• Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV

Study record dates

Study Major Dates

• Study Start (Estimated): March 23, 2026
• Primary Completion (Estimated): October 23, 2026
• Study Completion (Estimated): October 23, 2026

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Antiretroviral Therapy, Highly Active; HIV-1; Tenofovir Alafenamide; HIV Infections; Antiretroviral Therapy; Emtricitabine; Treatment Interruption; Phase 4; Bictegravir; Treatment-Experienced; B/F/TAF; Virologically Suppressed; Returning to Care; B/F/TAF; bictegravir, emtricitabine, tenofovir alafenamide, drug combination; Rapid Restart
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; bictegravir, emtricitabine, tenofovir alafenamide, drug combination
• Other Study ID Numbers: CAN-MID-REINITIATE-01; CO-US-380-7671 (Other Grant/Funding Number: Gilead Sciences); CO-US-380-7672 (Other Grant/Funding Number: Gilead Sciences)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) from this study will not be made available to other researchers. This decision is based on considerations related to the vulnerability of the study population and the need to uphold the highest standards of data protection and confidentiality. Given that participants are living with HIV-1, which is a condition associated with significant social, legal, and personal sensitivities, sharing IPD could increase the risk of inadvertent disclosure of sensitive personal information. Ensuring the privacy and protection of identities and health data of participants is essential; therefore, we have decided not to make IPD available for other researchers' use.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No