Phd in ADVANCES IN INFECTIOUS DISEASES, MICROBIOLOGY, LEGAL
MEDICINE AND PUBLIC HEALTH SCIENCES

Thesis title: Virological efficacy, immunological impact, and quality of life in People Living with HIV treated with Long-Acting Injectable Cabotegravir/Rilpivirine: a holistic approach

Background: Long-acting injectable cabotegravir/rilpivirine (LAI CAB/RPV) represents a novel antiretroviral strategy designed to improve adherence, reduce pill burden, and enhance the quality of life of people living with HIV (PWH). Despite its proven virologic efficacy, limited data are available regarding its immunological, metabolic, and psychosocial impact in real-world settings. This study aimed to evaluate longitudinally the viro-immunologic, metabolic, and patient-reported outcomes (PROs) of PWH initiating LAI CAB/RPV compared with individuals maintained on oral antiretroviral therapy (ART). Methods: This prospective, observational study was conducted between June 2023 and June 2025 at the AIDS Reference Center of the Infectious Diseases Unit, Santa Maria Goretti Hospital, Latina (Sapienza University of Rome). Thirty-nine PWH switched to LAI CAB/RPV and nineteen continued oral ART as controls. Clinical, biochemical, and immunologic parameters—including lymphocyte subsets, monocyte and dendritic cell subpopulations, and plasma markers of immune activation (sCD14, sCD163)—were assessed at baseline and at scheduled follow-up visits up to 52 weeks. PROs were evaluated using validated questionnaires (HIVDQoL, HSS, GAD-7, PHQ-9, IIEF/FSFI, HIVTSQ). Statistical analyses were performed using nonparametric tests, with p ≤ 0.05 considered significant. Results: At 52 weeks, 92% of participants maintained virologic suppression. A single virologic failure was associated with delayed dosing and emergent NNRTI and INSTI resistance mutations. No significant changes were observed in CD4+ or CD8+ lymphocyte counts. A significant reduction in intermediate and non-classical monocytes, alongside a rise in plasmacytoid dendritic cells, indicated partial immune rebalancing. Plasma sCD14 levels decreased significantly after 12 months, whereas sCD163 remained stable. Anthropometric measures (BMI, blood pressure, waist circumference) and renal and hepatic function remained unchanged, while total cholesterol and triglycerides showed a modest decline. PROs revealed higher treatment satisfaction with LAI CAB/RPV, though overall quality of life, anxiety, depression, and stigma scores remained stable. Conclusions: LAI CAB/RPV demonstrated sustained virologic efficacy and favorable immunologic and metabolic profiles over 52 weeks, with high patient satisfaction. These findings support the long-term safety and acceptability of long-acting injectable ART and highlight its potential role in improving individualized HIV management and reducing residual inflammation in virologically suppressed individuals. Extending the follow-up period and increasing the study sample may allow these encouraging trends to reach statistical significance, providing stronger evidence for the long-term clinical and psychosocial advantages of LAI CAB/RPV in people living with HIV.