Efficacy of Long-Acting Injectable Cabotegravir and Rilpivirine Compared With Daily Oral Antiretroviral Therapy in Patients With HIV: A Systematic Review

Long-acting antiretroviral therapy (ART) has emerged as an innovative strategy to address limitations associated with daily oral regimens in people living with human immunodeficiency virus type 1 (HIV-1), including adherence barriers, treatment fatigue, and social stigma. This systematic review, conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and registered in International Prospective Register of Systematic Reviews (PROSPERO, CRD420251155009), identified randomized clinical trials comparing long-acting injectable cabotegravir and rilpivirine (CAB/RPV-LA) with standard daily oral ART through searches of PubMed, ScienceDirect, the Cochrane Library, and Google Scholar. Ten randomized trials involving 5,619 adults with HIV-1 were included. CAB/RPV-LA, administered intramuscularly every four or eight weeks, achieved durable virological suppression exceeding 90% across follow-up periods of 48 to 240 weeks, demonstrating non-inferiority to daily oral ART. Patient-reported outcomes consistently favored the injectable regimen, with higher treatment satisfaction scores and excellent adherence within the dosing window, while adverse events were mainly mild-to-moderate injection-site reactions (ISRs), resulting in treatment discontinuation in fewer than 1% of participants. Overall, the certainty of evidence was high for virological efficacy and moderate for safety and satisfaction outcomes, supporting long-acting CAB/RPV-LA as an effective and well-tolerated alternative that improves adherence, convenience, and quality of life in long-term HIV management.