Long-Term Real-World Evidence Study to Evaluate Effectiveness, Persistence, Adherence, Safety and Tolerability of Long-acting Cabotegravir Plus Rilpivirine.

RETROSPECTIVE AND PROSPECTIVE MULTICENTER STUDY EVALUATING LONG TERM EFFECTIVENESS AND SAFETY OF CABOTEGRAVIR AND RILPIVIRINE IN REAL LIFE AS A LONG-ACTING TREATMENT IN PEOPLE LIVING WITH HIV AFTER ITS IMPLEMENTATION IN SPAIN. RELATIVITY COHORT

The RELATIVITY study is a nationwide, multicenter, ambispective observational cohort evaluating the long-term effectiveness, safety, persistence, and tolerability of long-acting injectable cabotegravir plus rilpivirine (CAB+RPV LA) in people living with HIV in Spain.

The study includes adults with HIV-1 infection who achieved virological suppression on oral antiretroviral therapy and switched to long-acting CAB+RPV as part of routine clinical care. No study-specific treatment or interventions are performed. Clinical information is collected retrospectively from treatment initiation and prospectively during routine follow-up.

The primary objectives are to evaluate long-term virological effectiveness, treatment persistence, and confirmed virological failure over five years. Secondary objectives include assessment of safety, treatment discontinuation, adherence to injection schedules, immunological outcomes, metabolic changes, patient-reported outcomes, and factors associated with treatment success or failure. The study also evaluates outcomes in clinically relevant subgroups, including older adults, women, migrants, people with obesity, individuals with multimorbidity, and those infected through vertical transmission.

The RELATIVITY cohort is a national, multicenter, ambispective, non-interventional observational study designed to evaluate the long-term real-world effectiveness, safety, persistence, adherence, and tolerability of long-acting injectable cabotegravir plus rilpivirine (CAB+RPV LA) following its implementation into routine HIV care in Spain.

The study includes adults with HIV-1 infection who were virologically suppressed on oral antiretroviral therapy and switched to CAB+RPV LA according to routine clinical practice and approved prescribing information. Treatment decisions are entirely independent of study participation. No investigational intervention, randomization, or protocol-mandated treatment procedures are performed.

Participants receiving at least one injection of CAB+RPV LA between January 2023 and December 2024 are included through retrospective data collection, followed by prospective observation for up to five years after treatment initiation. Clinical data are collected from electronic medical records and entered into a centralized electronic case report form (eCRF). Follow-up reflects routine clinical practice at each participating center.

The primary study objectives are to evaluate:

Long-term maintenance of virological suppression. Treatment persistence. Time to confirmed virological failure.

Secondary objectives include evaluation of:

Safety and tolerability, including adverse events and injection-site reactions. Reasons for treatment discontinuation. Adherence to scheduled injection visits and oral bridging strategies. Virological rebounds and emergence of resistance-associated mutations. Immunological evolution (CD4 count, CD8 count, CD4/CD8 ratio). Changes in metabolic, renal, and hepatic parameters. Health-related quality of life and treatment satisfaction in a subset of participants.

Exploratory analyses will evaluate outcomes in clinically important subgroups, including older adults, women, migrants, individuals with obesity, multimorbidity, vertical HIV transmission, baseline resistance testing availability, and patients with previous adherence challenges to oral antiretroviral therapy.

Approximately 4,000 participants from 58 hospitals across Spain are expected to be included, making RELATIVITY one of the largest real-world cohorts evaluating long-acting injectable antiretroviral therapy. The study aims to generate robust evidence on the long-term use of CAB+RPV LA in routine clinical practice and to complement findings from randomized clinical trials by evaluating broader and more representative patient populations

Inclusion Criteria:

• Adults aged ≥18 years.
• Documented HIV-1 infection.
• Receiving oral antiretroviral therapy with plasma HIV-1 RNA <50 copies/mL at the time of switching to long-acting cabotegravir plus rilpivirine (CAB+RPV LA).
• No current or previous evidence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) or integrase strand transfer inhibitors (INSTIs), and no previous virological failure with these drug classes.
• Received at least one injection of CAB+RPV LA before January 1, 2025.
• Able to understand and provide written informed consent.

Exclusion Criteria:

• Any contraindication to CAB+RPV LA according to the approved product labeling.
• Previous exposure to long-acting CAB+RPV within an interventional clinical trial.
• Active hepatitis B infection (HBsAg positive).
• Pregnancy or breastfeeding.