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

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.

• Cabotegravir Plus Rilpivirine Long-Acting Injectable (Drug), also known as CAB/RPV LA, Long-Acting Cabotegravir and Rilpivirine, Cabotegravir + Rilpivirine: 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.

Primary outcomes

• Virologic Suppression at Follow-Up [Up to 24 months after initiation of CAB/RPV LA]: 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.

Secondary outcomes

• Treatment Persistence on CAB/RPV LA [Up to 24 months after initiation of 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.
• Treatment Discontinuation Rate [Up to 24 months after initiation of CAB/RPV LA]: 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.
• Time to Treatment Discontinuation [Up to 24 months after initiation of CAB/RPV LA]: Median time from first administration of CAB/RPV LA to permanent discontinuation of the regimen, calculated using available clinical records.
• Adherence to Injection Schedule [Up to 24 months after initiation of CAB/RPV LA]: 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.
• Delayed or Missed Injections [Up to 24 months after initiation of CAB/RPV LA]: 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.
• Confirmed Virologic Failure (CVF) [Up to 24 months after initiation of CAB/RPV LA]: 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.
• Viral Rebound [Up to 24 months after initiation of CAB/RPV LA]: 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.
• Virologic Non-Response After CVF [Up to 24 months after initiation of CAB/RPV LA]: Proportion of participants who do not achieve re-suppression (HIV-1 RNA <50 copies/mL) following confirmed virologic failure during the follow-up period.

Sex: All, ages: 18 Years to any

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