rilpivirine
Regulatory sources consulted
Approved indications
- Combination treatment of HIV-1 without NNRTI resistance mutations in patients aged 12 years and older and weighing at least 35 kg with baseline viral load ≤100,000 copies/mL.
Contraindications
Absolute
- Hypersensitivity to rilpivirine.
- Concomitant proton-pump inhibitors, rifampicin or rifapentine, inducing anticonvulsants, repeated systemic dexamethasone, or St John’s wort.
Clinical warnings
- It may cause severe skin reactions or DRESS, hepatotoxicity, and depressive disorders; stop and assess severe symptoms. — CIMA/AEMPS, ficha técnica 11736001
- Major warning · Supratherapeutic doses prolong QT; avoid torsades-risk combinations when alternatives exist. — CIMA/AEMPS, ficha técnica 11736001
Drug interactions
- HighAntacids and H2 antagonists
Mechanism: Higher gastric pH reduces rilpivirine absorption.
Recommendation: Give antacids at least 2 hours before or 4 hours after; give H2 antagonists at least 12 hours before or 4 hours after.
CIMA/AEMPS, ficha técnica 11736001
- ModerateCYP3A inducers
Mechanism: They markedly reduce rilpivirine and may cause virologic failure.
Recommendation: Do not combine with contraindicated inducers.
CIMA/AEMPS, ficha técnica 11736001
Adverse events
Common (≥1%)
Depression, insomnia, headache, dizziness, nausea, and increased transaminases
Rare but serious
DRESS, severe skin reaction, severe hepatotoxicity, and suicidal ideation
Pregnancy and lactation
Rilpivirine exposure decreases during pregnancy; use is preferably avoided, and if continued, monitor viral load continuously. Do not breastfeed during HIV treatment.
Recent literature (PubMed)
Intramuscular injection of long-acting cabotegravir and rilpivirine is a novel, long-acting antiretroviral therapy (ART) combination approved for use as a fully suppressive regimen for people living with HIV. Long-acting cabotegravir with rilpivirine ART has reduced required dosing frequency from once daily to once every month or every 2 months injections. This new era of long-acting ART, which includes other antiretrovirals and formulations in various stages of clinical development, holds tremendous promise to change the standard of HIV treatment. Although long-acting ART has high potential to be revolutionary in the landscape of HIV care, prevention, and treatment cascade, more data are needed to substantiate its efficacy and cost-effectiveness among patients at risk of non-adherence and across age groups, pregnancy, and post partum. Advocacy efforts and policy changes to optimise a sustained, high-quality, equitable reach of long-acting ART, especially in low-income and middle-income countries where most people living with HIV reside, are needed to realise the full benefits of long-acting ART. Cabotegravir is an antiviral agent that inhibits the human immunodeficiency virus (HIV) integrase and is used in combination with rilpivirine, a non-nucleoside HIV reverse transcription inhibitor, in the treatment of HIV infection and the acquired immunodeficiency syndrome (AIDS). The fixed combination of cabotegravir and rilpivirine is typically given intramuscularly once monthly and has been linked to a low rate of serum aminotransferase elevations during therapy and to rare episodes of acute, clinically apparent liver injury.
- Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.
HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy. This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection. PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework. We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I2=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I2=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decrea
Cabotegravir plus rilpivirine is the only approved complete long-acting regimen for the maintenance of HIV-1 virological suppression dosed every 2 months. The SOLAR study aimed to compare long-acting cabotegravir plus rilpivirine every 2 months with continued once-daily bictegravir, emtricitabine, and tenofovir alafenamide for the maintenance of HIV-1 virological suppression in adults living with HIV. SOLAR is a randomised, open-label, multicentre, phase 3b, non-inferiority study. The study was done in 118 centres across 14 countries. Participants with HIV-1 RNA less than 50 copies per mL were randomly assigned (2:1), stratified by sex at birth and BMI, to either long-acting cabotegravir (600 mg) plus rilpivirine (900 mg) dosed intramuscularly every 2 months or to continue daily oral bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg). Participants randomly assigned to long-acting therapy had a choice to receive cabotegravir (30 mg) plus rilpivirine (25 mg) once daily as an optional oral lead-in for approximately 1 month. The primary efficacy endpoint was the proportion of participants with virological non-response (HIV-1 RNA ≥50 copies per mL; the US Food and Drug Administration snapshot algorithm, 4% non-inferiority margin; modified intention-to-treat exposed population) at month 11 (long-acting start with injections group) and month 12 (long-acting with oral lead-in group and bictegravir, emtricitabine, and tenofovir alafenamide group). The study is registered with ClinicalTrials.gov, NCT04542070, and is ongoing. 837 participants were screened between Nov 9, 2020, and May 31, 2021, and 687 were randomly assigned to switch treatment or continue existing treatment. Of 670 participants (modified intention-to-treat exposed population), 447 (67%) switched to long-acting therapy (274 [61%] of 447 start with injections; 173 [39%] of 447 with oral lead-in) and 223 (33%) continued bictegravir, emtricitabine, and tenofovir alafenamide. Baseline c