cabotegravir
Regulatory sources consulted
Approved indications
- HIV-1 pre-exposure prophylaxis in adults and adolescents weighing at least 35 kg who test negative, as oral lead-in or bridging for the long-acting cabotegravir regimen.
Contraindications
Absolute
- Hypersensitivity to cabotegravir.
- Positive or unknown HIV status for pre-exposure prophylaxis.
- Rifampicin, rifapentine, carbamazepine, oxcarbazepine, phenytoin, or phenobarbital
Clinical warnings
- Confirm HIV-negative status before starting and before each continuation; using PrEP during undiagnosed infection may select resistance. — CIMA/AEMPS, ficha técnica 1231760001
- Major warning · It may cause hepatotoxicity, hypersensitivity, and depressive disorders; stop and assess severe symptoms. — CIMA/AEMPS, ficha técnica 1231760001
- Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported; stop immediately and do not restart cabotegravir after a severe skin reaction. — CIMA/AEMPS, ficha técnica 1231760001
Drug interactions
- ModerateRifampicin, rifapentine, carbamazepine, oxcarbazepine, phenytoin, or phenobarbital
Mechanism: UGT1A1/UGT1A9 induction reduces cabotegravir and may cause loss of efficacy.
Recommendation: Do not combine.
CIMA/AEMPS, ficha técnica 1231760001
- ModerateAntacids containing polyvalent cations
Mechanism: They may reduce oral cabotegravir absorption.
Recommendation: Give at least 2 hours before or 4 hours after.
CIMA/AEMPS, ficha técnica 1231760001
Adverse events
Common (≥1%)
Headache, diarrhea, nausea, fatigue, and abnormal dreams
Rare but serious
Hypersensitivity, hepatotoxicity, and suicidal behavior
Pregnancy and lactation
It is not recommended during pregnancy unless benefit outweighs risk. During breastfeeding, use only if expected benefit outweighs risk to the infant.
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.
Pre-exposure prophylaxis (PrEP) of human immunodeficiency virus (HIV) represents the most significant breakthrough in the HIV prevention field over the past decade. PrEP is an effective strategy in preventing the transmission of HIV across all populations, providing high adherence. The current PrEP options include oral daily and on-demand tenofovir-based regimens, long-acting injections of cabotegravir, and a 1-month dapivirine vaginal ring. As a component of a multifaceted prevention approach, extensive deployment of PrEP holds the promise to significantly reduce the global HIV epidemic. Nonetheless, barriers still exist in terms of uptake, adherence, and persistence, while disparities in PrEP accessibility remain a concern. 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