Rilpivirine 900mg/3ml prolonged-release suspension for injection vials

Abstract Background In 2023, there were 39.9 million people living with HIV (PLWH) worldwide and 630 000 deaths related to HIV. New strategies are needed, and long-acting antiretrovirals (LAAs) are now widely considered to have great potential to help end the HIV epidemic. This systematic review and meta-analysis compare the safety and efficacy of LAA versus standard oral treatment (SOT) for HIV. Methods PubMed and Embase databases, supplemented by ClinicalTrials.gov and grey literature, were searched. Randomized controlled trials (RCTs) reporting efficacy and/or safety of LAA versus SOT for PLWH until June 2024 were included. Efficacy (HIV RNA < 50 copies/mL) and HIV RNA ≥ 50 copies/mL, adverse events (AEs), treatment discontinuation, CD4 count, metabolic parameters and drug resistance were assessed. Prespecified subgroup analyses were conducted. The risk of bias was assessed with Cochrane RoB 2.0. Certainty of evidence was assessed using GRADE. Results Six RCTs were eligible for inclusion, involving 2829 participants. LAA was non-inferior to SOT in suppressing HIV RNA < 50 copies/mL [Risk Difference (RD), −0.00; 95% CI, −0.03–0.02; P = 0.83; I2 = 51%; high quality of evidence (QoE)]. LAA was associated with higher drug resistance (percentage pooled estimate, 57%; 95% CI, 33%–78% versus 9%; 95% CI, 2%–30%; moderate QoE) and risk of grade 1–4 AEs than SOT [Risk Ratio (RR), 1.22; 95% CI, 1.12–1.33; P < 0.001; I2 = 62%; moderate QoE]. Conclusions LAA has non-inferior efficacy compared to SOT. However, participants receiving LAA were at a higher risk of developing drug resistance, cross-resistance and AEs.

Abstract licence: CC BY

Randomized controlled trial evidence suggests that long‐acting injectable (LA‐I) cabotegravir and rilpivirine (CAB+RPV) has similar virological failure (VF) rates to daily oral therapy, but clinical practice evidence is lacking. Integrase inhibitor (INI) resistance may limit future therapy. The optimal regimen is uncertain.

Abstract licence: CC BY

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.

Abstract licence: CC BY