Long-Acting Cabotegravir and Rilpivirine in People Living With HIV-1 Subtype A6: A Real-World Retrospective Study (LACRIS)

Long-Acting Cabotegravir And Rilipivirine In People Living With HIV-1 Subtype A6. A Multicentre Real-world, Retrospective Matched Case Study

This study evaluates the real-world effectiveness and safety of a long-acting injectable HIV treatment consisting of cabotegravir and rilpivirine in people living with HIV-1. The focus is on individuals with HIV-1 subtype A6, which is common in Eastern Europe and among people who acquired HIV in that region, and on comparison with individuals with subtype B and those with an unknown subtype.

Although long-acting cabotegravir and rilpivirine are widely used and effective, limited real-world data are available on how well this treatment works in people with HIV-1 subtype A6. This is important because subtype A6 has been suggested as a potential risk factor for treatment failure, but current evidence is inconclusive.

The study uses existing medical records from treatment centers in Poland, Germany, and the Czech Republic. It includes adults with HIV who have received at least one injection of long-acting cabotegravir and rilpivirine and follows their clinical outcomes for up to 24 months. Researchers will assess viral suppression, treatment persistence, adherence to injection schedules, and reasons for treatment discontinuation.

The results of this study will help clinicians better understand whether HIV-1 subtype A6 affects treatment outcomes and whether knowing a patient's HIV subtype is important when deciding to switch to long-acting injectable therapy. The findings may support safer and more effective use of this treatment in diverse patient populations.

Study Overview

• Status: Not yet recruiting
• Conditions: Human Immunodeficiency Virus (HIV)-1 Infection; HIV-1 Subtype A6 Infection; HIV-1 Subtype B Infection; Virologically Suppressed HIV-1 Infection Receiving Long-Acting Antiretroviral Therapy
• Intervention / Treatment: Drug: Cabotegravir Plus Rilpivirine Long-Acting Injectable

Detailed Description

This is a multicentre, international, real-world, retrospective observational study designed to evaluate clinical outcomes of long-acting injectable cabotegravir plus rilpivirine (CAB/RPV LA) in adults living with HIV-1. The study is conducted at HIV treatment centers in Poland, Germany, and the Czech Republic and is based on routinely collected clinical data from electronic medical records and paper charts.

The study population includes treatment-experienced individuals aged 18 years or older who received at least one dose of CAB/RPV LA in routine clinical practice. Participants are grouped according to HIV-1 subtype: subtype A6, subtype B, and unknown subtype. Individuals with known subtype A6 are matched with individuals with subtype B using propensity score matching to reduce the impact of confounding factors. Participants with unknown subtype are analyzed as an unmatched group.

Clinical data are collected from the time of CAB/RPV LA initiation (index date) and from follow-up visits closest to 6, 12, 18, and 24 months after initiation. Outcomes assessed include treatment persistence, adherence to injection schedules, discontinuation rates and reasons for discontinuation, and measures of virologic effectiveness. Virologic outcomes include viral suppression, viral rebound, and confirmed virologic failure as defined by standard HIV RNA criteria.

For participants with unknown HIV-1 subtype, proviral DNA genotyping is performed after initial descriptive analyses to explore whether knowledge of HIV-1 subtype has prognostic relevance for clinical outcomes. Genotypic data are analyzed descriptively and may inform additional exploratory analyses.

As this is a retrospective, non-interventional study using existing clinical data, no study-specific treatment interventions are performed. Safety data collection is limited to adverse events leading to treatment discontinuation, reflecting routine clinical practice. The study aims to provide clinically relevant real-world evidence on the use of CAB/RPV LA across different HIV-1 subtypes, with particular focus on subtype A6.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Miłosz Parczewski, prof. dr hab. n. med.; Phone Number: +48 91 813 94 41; Email: klinzak@pum.edu.pl
• Study Contact Backup: Name: Karolina Sorbian-Gajewska

Study Locations

• Poland
  • West Pomeranian Voivodeship
    • Szczecin, West Pomeranian Voivodeship, Poland, 71-455
      • Katedra Chorób Zakaźnych i Niedoborów Immunologicznych
      • Contact: Miłosz Parczewski, prof. dr hab. n. med.; Phone Number: +48 91 813 94 41; Email: klinzak@pum.edu.pl

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adults aged 18 years or older living with HIV-1 infection who have received long-acting injectable cabotegravir plus rilpivirine (CAB/RPV LA) as part of routine clinical care. Participants are treatment-experienced and include individuals with suppressed or unsuppressed HIV-1 viral load at the time of treatment initiation.

Patients are identified retrospectively from electronic medical records at participating HIV treatment centers in Poland, Germany, and the Czech Republic. Participants are grouped according to documented HIV-1 subtype (subtype A6, subtype B, or unknown subtype). Individuals with known subtype A6 are matched with individuals with subtype B based on selected clinical characteristics, while participants with unknown subtype are analyzed as an unmatched descriptive cohort.

The study includes a broad, real-world patient population without upper age limits or sex-based restrictions, reflecting routine clinical practice in participating ce

Description

Inclusion Criteria:

• Confirmed diagnosis of HIV-1 infection
• Age ≥18 years at the time of initiation of long-acting cabotegravir plus rilpivirine (CAB/RPV LA)
• Received at least one dose of CAB/RPV LA as part of routine clinical care
• Availability of relevant clinical data in medical records for retrospective analysis
• Signed informed consent for use of clinical data
• Agreement to provide an additional blood sample for proviral DNA genotyping, if HIV-1 subtype was unknown at treatment initiation

Exclusion Criteria:

- Lack of patient consent for use of clinical data for research purposes

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HIV-1 subtype A6; This cohort includes adults living with HIV-1 with a confirmed subtype A6 infection who received at least one dose of long-acting injectable cabotegravir plus rilpivirine (CAB/RPV LA) as part of routine clinical care. Participants are treatment-experienced and include individuals with suppressed or unsuppressed viral load at treatment initiation. Clinical outcomes, including virologic effectiveness, treatment persistence, adherence, and discontinuation, are assessed retrospectively using existing medical records. This cohort is matched with the subtype B cohort using propensity score methods.	Drug: Cabotegravir Plus Rilpivirine Long-Acting Injectable; Cabotegravir plus rilpivirine long-acting (CAB/RPV LA) is a complete antiretroviral regimen administered as intramuscular injections and approved for the maintenance treatment of HIV-1 infection in adults. In this observational, retrospective study, CAB/RPV LA is used as part of routine clinical care and is not assigned by the study protocol. Participants received CAB/RPV LA according to local prescribing information, including dosing intervals and injection windows. The study evaluates real-world clinical outcomes of CAB/RPV LA across different HIV-1 subtype groups (subtype A6, subtype B, and unknown subtype). Outcomes of interest include virologic effectiveness, treatment persistence, adherence to injection schedules, and treatment discontinuation. No study-specific modifications to dosing, administration, or clinical management are performed.; Other Names: CAB/RPV LA; Long-Acting Cabotegravir and Rilpivirine; Cabotegravir + Rilpivirine
HIV-1 Subtype B Cohort; This cohort consists of adults living with HIV-1 with a confirmed subtype B infection who received long-acting injectable cabotegravir plus rilpivirine (CAB/RPV LA) in routine clinical practice. Participants are selected and matched to the subtype A6 cohort based on predefined confounding variables, including age, gender, body mass index category, and CD4 cell nadir. Outcomes are evaluated retrospectively to provide a comparative real-world context for the subtype A6 cohort.	Drug: Cabotegravir Plus Rilpivirine Long-Acting Injectable; Cabotegravir plus rilpivirine long-acting (CAB/RPV LA) is a complete antiretroviral regimen administered as intramuscular injections and approved for the maintenance treatment of HIV-1 infection in adults. In this observational, retrospective study, CAB/RPV LA is used as part of routine clinical care and is not assigned by the study protocol. Participants received CAB/RPV LA according to local prescribing information, including dosing intervals and injection windows. The study evaluates real-world clinical outcomes of CAB/RPV LA across different HIV-1 subtype groups (subtype A6, subtype B, and unknown subtype). Outcomes of interest include virologic effectiveness, treatment persistence, adherence to injection schedules, and treatment discontinuation. No study-specific modifications to dosing, administration, or clinical management are performed.; Other Names: CAB/RPV LA; Long-Acting Cabotegravir and Rilpivirine; Cabotegravir + Rilpivirine
HIV-1 Subtype Unknown Cohort; This cohort includes adults living with HIV-1 who received long-acting injectable cabotegravir plus rilpivirine (CAB/RPV LA) and had no documented HIV-1 subtype at the time of treatment initiation. Participants are analyzed as an unmatched descriptive group. Retrospective clinical outcome data are collected from medical records. For selected participants, proviral DNA genotyping from blood samples is performed after initial analyses to explore the clinical relevance of HIV-1 subtype knowledge prior to switching to long-acting injectable therapy.	Drug: Cabotegravir Plus Rilpivirine Long-Acting Injectable; Cabotegravir plus rilpivirine long-acting (CAB/RPV LA) is a complete antiretroviral regimen administered as intramuscular injections and approved for the maintenance treatment of HIV-1 infection in adults. In this observational, retrospective study, CAB/RPV LA is used as part of routine clinical care and is not assigned by the study protocol. Participants received CAB/RPV LA according to local prescribing information, including dosing intervals and injection windows. The study evaluates real-world clinical outcomes of CAB/RPV LA across different HIV-1 subtype groups (subtype A6, subtype B, and unknown subtype). Outcomes of interest include virologic effectiveness, treatment persistence, adherence to injection schedules, and treatment discontinuation. No study-specific modifications to dosing, administration, or clinical management are performed.; Other Names: CAB/RPV LA; Long-Acting Cabotegravir and Rilpivirine; Cabotegravir + Rilpivirine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic Suppression at Follow-Up	Proportion of participants with HIV-1 RNA viral load <50 copies/mL at follow-up after initiation of long-acting cabotegravir plus rilpivirine (CAB/RPV LA), assessed using available clinical laboratory measurements. Virologic suppression will be evaluated at approximately 6, 12, 18, and 24 months after treatment initiation, with last observation carried forward where applicable.	Up to 24 months after initiation of CAB/RPV LA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Persistence on CAB/RPV LA	Proportion of participants who remain on long-acting cabotegravir plus rilpivirine (CAB/RPV LA) at each follow-up time point after initiation, based on documentation of continued injections in routine clinical care.	Up to 24 months after initiation of CAB/RPV LA
Treatment Discontinuation Rate	Proportion of participants who discontinue CAB/RPV LA after initiation, including documentation of the reason for discontinuation such as adverse events, virologic failure, or other clinical or patient-related reasons.	Up to 24 months after initiation of CAB/RPV LA
Time to Treatment Discontinuation	Median time from first administration of CAB/RPV LA to permanent discontinuation of the regimen, calculated using available clinical records.	Up to 24 months after initiation of CAB/RPV LA
Adherence to Injection Schedule	Adherence to the CAB/RPV LA dosing schedule, assessed as the proportion of participants receiving injections within the allowed ±7-day dosing window relative to the target injection date.	Up to 24 months after initiation of CAB/RPV LA
Delayed or Missed Injections	Proportion of participants with delayed injections (>7 days after target date), missed injections, and the number and duration of delayed or missed injections during follow-up.	Up to 24 months after initiation of CAB/RPV LA
Confirmed Virologic Failure (CVF)	Proportion of participants meeting criteria for confirmed virologic failure, defined as two consecutive HIV-1 RNA measurements ≥200 copies/mL, or one HIV-1 RNA ≥200 copies/mL followed by treatment discontinuation within four months.	Up to 24 months after initiation of CAB/RPV LA
Viral Rebound	Proportion of participants experiencing viral rebound, including viral blips (single HIV-1 RNA 50-199 copies/mL followed by <50 copies/mL), low-level viremia (two consecutive measurements 50-199 copies/mL), or viremia >200 copies/mL not leading to treatment discontinuation.	Up to 24 months after initiation of CAB/RPV LA
Virologic Non-Response After CVF	Proportion of participants who do not achieve re-suppression (HIV-1 RNA <50 copies/mL) following confirmed virologic failure during the follow-up period.	Up to 24 months after initiation of CAB/RPV LA

Collaborators and Investigators

• Sponsor: Pomeranian Medical University Szczecin
• Collaborators: ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 19, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: HIV-1; Rilpivirine; Cabotegravir; Retrospective Study; Virologic Failure; Real-World Study; Long-Acting Antiretroviral Therapy; CAB/RPV LA; HIV-1 Subtype A6; HIV-1 Subtype B; Virologic Suppression; Injectable HIV Therapy; Treatment Persistence
• 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; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Nitriles; Rilpivirine; cabotegravir
• Other Study ID Numbers: LACRIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared because this is a retrospective, observational study based on routinely collected clinical data from multiple centers. The data are pseudo-anonymized and subject to local data protection regulations and ethical approvals, which limit the ability to share individual-level data outside the study team.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No