Cabenuva (cabotegravir long acting/rilpivirine long acting) / J&J, GSK, ViiV Healthcare, Pfizer, Shionogi - LARVOL DELTA

Preclinical evaluation of long-acting cabotegravir and rilpivirine for HIV post-exposure prophylaxis in a macaque model. (PubMed, EBioMedicine) - "We document protection in macaques by one-time CAB LA/RPV LA PEP under highly stringent modeling conditions. Delayed breakthrough infections highlight potential diagnostic challenges associated with this PEP modality and underscore the need for prolonged follow-up."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

IM-CAPABLE: IMplementation of CAB+RPV LA for People With HIV in Non-Metropolitan Areas (clinicaltrials.gov) - P=N/A | N=55 | Recruiting | Sponsor: University of Nebraska | Trial completion date: Apr 2026 ➔ Apr 2027 | Trial primary completion date: Apr 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Efficacy and Safety of Cabotegravir-Rilpivirine in PLWH: A Real-World Study. (PubMed, Viruses) - "CAB + RPV demonstrated high efficacy and tolerability in a real-world setting, with favorable immunological and metabolic outcomes. These findings support its use as a viable therapeutic option for PLWH, especially those with adherence barriers. Further long-term studies are warranted to confirm these results across broader populations."

Clinical • Journal • Real-world evidence • Retrospective data • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Long-Acting Cabotegravir/Rilpivirine for HIV Antiretroviral Therapy Throughout Pregnancy: A Case Report and Literature Review. (PubMed, Case Rep Infect Dis) - "Benefits of CAB/RPV during pregnancy include improved drug adherence and discretion. Based on our experience and review of the literature, long-acting intramuscular CAB/RPV may be of value in treatment-experienced patients experiencing difficulties with pill adherence."

Journal • Cardiovascular • CNS Disorders • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Nephrology • Ventriculomegaly

Impact of Gluteal Injection Site on Pharmacokinetics and Tolerability of Antiretroviral Therapy with Long-Acting Cabotegravir and Rilpivirine. (PubMed, AIDS Patient Care STDS) - "Ventrogluteal administration is associated with more consistent pharmacokinetics and improved tolerability, supporting its use as the preferred site for long-acting CAB/RPV. Although CAB trough levels were modestly lower and occasionally fell below predefined thresholds with VG injection, this did not impact virologic outcomes, reinforcing its clinical suitability in most settings."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

The effect of long-acting cabotegravir and rilpivirine treatment on drug resistance in South Africa: a modelling study. (PubMed, Lancet Glob Health) - "LAI cabotegravir and rilpivirine roll-out in South Africa should be cautious and targeted. Resistance risks may be mitigated through pre-treatment resistance testing, close monitoring of treatment outcomes, and efforts to increase retention in care."

Journal • Allergy • Human Immunodeficiency Virus • Immunology • Infectious Disease

Virological Success With Long-Acting Cabotegravir and Rilpivirine Despite Historical Rilpivirine Resistance: A Real-World Case Series. (PubMed, Open Forum Infect Dis) - "Twelve were virologically suppressed at switch. No virological failures occurred, supporting cautious CAB/RPV use in selected patients with remote or polymorphic mutations."

Clinical • Journal • Real-world evidence

Cabotegravir and rilpivirine for treatment of HIV infection in Africa: week 96 results from the phase 3b randomized, open-label, noninferiority CARES trial. (PubMed, Nat Med) - "Cabotegravir and rilpivirine long-acting therapy produced durable virologic suppression, met the prespecified noninferiority endpoint compared with oral therapy and demonstrated an acceptable safety and tolerability profile. Long-acting therapy may be considered for use in African treatment programs. PACTR registration: 202104874490818."

Head-to-Head • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease

Genotyping not required for sustained effectiveness of long-acting cabotegravir plus rilpivirine: evidence from the RELATIVITY cohort. (PubMed, AIDS) - "In this large real-world cohort, the absence of genotypic data did not affect LAI CAB+RPV effectiveness in virologically suppressed PWH. Limitations, including ambispective design, short follow-up, and low non-B subtype prevalence, may limit generalizability."

Journal • Human Immunodeficiency Virus • Infectious Disease

Durability of Two-Drug Antiretroviral Regimens as Maintenance Therapy in People Living with HIV and Reasons for Switch to a Three-Drug Regimen: A Real-Life Cohort Study. (PubMed, AIDS Patient Care STDS) - "Dolutegravir (DTG) or ritonavir-boosted protease inhibitor (PI/r)-based 2DR were the most frequently prescribed regimens, respectively, in 64% and 16% of cases. Sixty-nine patients (12%) received injectable long-acting cabotegravir-rilpivirine...Our study showed that 2DR was a sustainable simplification strategy in a real-life setting. The return to 3DR was significantly impacted by the prescription of 2DR in patients heavily pre-treated."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Investigating the Role of Proviral Sequencing When Transitioning Virally Suppressed Adults with HIV to Long-Acting Injectable Cabotegravir-Rilpivirine (AMP 2025) - "Using our clinical eligibility review process, proviral sequencing was limited to 15% of LAI CAB/RPV referrals and, when obtained, provided clinically actionable information. Although interpretation of RPV RAMs was consistent, interpretation of CAB RAMs evolved during the study period and must continue to adapt as the use of integrase inhibitor-based regimens increases worldwide. Overall, our experience provides an important example of using patient risk factors to inform proviral sequencing when starting LAI CAB/RPV."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Long-acting Cabotegravir/Rilpivirine for Treatment of HIV During Pregnancy: A Case Series. (PubMed, Open Forum Infect Dis) - "We present pharmacokinetic data on long-acting cabotegravir/rilpivirine (LA CAB/RPV) from two patients during their second and third trimesters. Monthly LA CAB/RPV dosing maintained concentrations above the proposed efficacy thresholds while bimonthly dosing resulted in subtherapeutic RPV concentrations. This highlights the potential of monthly LA CAB/RPV dosing in pregnancy."

Journal • Human Immunodeficiency Virus • Infectious Disease

Risk of Severe Hepatotoxicity With Long-Acting Antiretroviral Therapy and Concomitant Acute Hepatitis B Infection: A Rare Clinical Observation (ACG 2025) - "Given clinical worsening, Biktarvy, effective against both infections, was started.Additional testing showed a ferritin level of 6,021 ng/ml with negative serologies for Hepatitis D, E, EBV, and CMV. Given the increased risk of severe hepatotoxicity with Cabenuva, particularly in the context of acute HBV infection, the need for long-term safety studies for injectable ART is paramount.Figure: Figure 1. Lab trends correlating with clinical events; CT abdomen and liver histology showing changes consistent with cirrhosis."

Clinical • Anorexia • Cardiovascular • Cholestasis • Fibrosis • Gastroenterology • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Liver Failure • Portal Hypertension • CD4

Cabotegravir and Rilpivirine concentrations and HIV-1 RNA suppression in genital fluids and rectum in people with HIV on long-acting intramuscular Cabotegravir plus Rilpivirine antiretroviral therapy. (PubMed, J Infect Dis) - P4 | "This study examined cabotegravir (CAB) and rilpivirine (RPV) distribution and HIV suppression in genital and rectal compartments after switching to long-acting intramuscular CAB+RPV administered every two months. All participants maintained HIV-1 RNA <20 copies/mL in all matrices. Clinical Trial Registration: EudraCT Number: 2021-006779-41."

Journal • Human Immunodeficiency Virus • Infectious Disease

High Virologic Suppression and Favorable Profiles of Two-Drug Antiretroviral Regimens in Africa: A Systematic Review of Current Evidence. (PubMed, Clin Pharmacol Ther) - "Regimens included dolutegravir-based (40%) and long-acting injectable cabotegravir+rilpivirine (CAB+RPV) (60%). Limitations included short follow-up, lack of blinding (80%), and potential selection bias (40%). Two-drug ART regimens appear effective and well-tolerated in African settings, warranting further high-quality, long-term studies."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • CD4

Third-Trimester HIV Viremia Treated With Long-Acting Cabotegravir and Rilpivirine: A Case Report. (PubMed, Open Forum Infect Dis) - "We report the first case to quantitatively demonstrate a rapid and substantial viral load reduction using long-acting cabotegravir and rilpivirine in the third trimester of pregnancy. This case underscores the challenges some pregnant individuals face with daily oral antiretroviral therapy and the potential role of long-acting injectables in select scenarios."

Journal • Human Immunodeficiency Virus • Infectious Disease

Exploring the Interaction Between Injection Site and Biological Sex on the Real-world Population Pharmacokinetics of Long-acting Cabotegravir and Rilpivirine in People With HIV. (PubMed, Open Forum Infect Dis) - "Subcutaneous depot deposition after intramuscular injections is not uncommon, occurring more frequently in females and is associated with increased skin to muscle thickness. Slower absorption of cabotegravir from subcutaneous administration contributes to the observed sex differences in drug concentrations."

Journal • PK/PD data • Real-world evidence • Human Immunodeficiency Virus • Infectious Disease

A prospective assessment of the efficacy and durability of long-acting cabotegravir and rilpivirine in individuals with HIV in Spain (RELATIVITY study). (PubMed, J Antimicrob Chemother) - "Interim results from the RELATIVITY cohort confirm high effectiveness and safety of LAI cabotegravir plus rilpivirine in Spanish clinical practice, consistent with randomized trial outcomes and real-world data. An extended follow-up will provide further insights."

Journal • Fatigue • Human Immunodeficiency Virus • Infectious Disease

Pharmacist-led Intervention for Injectable HIV Treatment for Women With Health-related Social Needs (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Yale University | Trial completion date: Oct 2025 ➔ Mar 2027 | Trial primary completion date: Oct 2025 ➔ Mar 2027

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Clinical outcomes of long-acting cabotegravir and rilpivirine in people with HIV aged 60 and older: Real-world data from the Spanish RELATIVITY cohort. (PubMed, HIV Med) - "In this large multicentre real-world sub-study, LAI CAB + RPV maintained virological control and showed good tolerability in older people with HIV despite high multi-morbidity and long-term ART exposure. These findings extend the evidence from previous trials and support LAI CAB + RPV as a feasible option for geriatric HIV care. Longer follow-up will provide further insights into durability and quality-of-life benefits."

Clinical data • Journal • Real-world evidence • Human Immunodeficiency Virus • Infectious Disease • CD4

Discontinuation of Long-acting Injectable Cabotegravir-Rilpivirine in a Large Clinic Cohort. (PubMed, Open Forum Infect Dis) - "Virologic failure and efficacy concerns drove discontinuation for people with HIV with adherence challenges. Most had viral suppression on alternate antiretrovirals post-discontinuation."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pain

Month 12 outcomes of switching to long-acting cabotegravir + rilpivirine with an oral lead-in versus continuing bictegravir/ emtricitabine/tenofovir alafenamide in the Phase 3b randomized SOLAR study. (PubMed, J Infect Chemother) - P3 | "Switching to CAB+RPV LA OLI demonstrated comparable efficacy to continuing BIC/FTC/TAF, was well tolerated and preferred by most participants who switched. ClinicalTrials.gov; NCT04542070 (https://clinicaltrials.gov/study/NCT04542070)."

Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease

Virological success with long-acting cabotegravir and rilpivirine in individuals with historical rilpivirine resistance: a real-world case series (EACS 2025) - "Conclusions : CAB/RPV LA maintained durable virological suppression in individuals with historical RPV RAMs, including E138A. These real-world findings support cautious use in well-selected persons with remote NNRTI resistance."

Clinical • Late-breaking abstract • Real-world • Real-world evidence • Human Immunodeficiency Virus • Infectious Disease

'Ask Us’ Europe, a community co-produced study: PLWH perspectives on treatment optimisation discussions with healthcare providers in 18 countries- an interim analysis (EACS 2025) - "Purpose : Despite significant interest in long-acting modalities, long-acting injectable cabotegravir + rilpivirine (CAB+RPV) usage is low across Europe, suggesting a gap between interest and practice...Conclusions : Most people did not discuss treatment optimisation in the past year and among those who had, CAB+RPV was not necessarily discussed. Healthcare provider-initiated discussions on CAB+RPV seemed to strongly influence CAB+RPV provision."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

High Effectiveness and Rare Virologic Failure in Treatment-Experienced Individuals on Long-Acting Cabotegravir + Rilpivirine Therapy Across Europe: Insights from the EuroSIDA Study (EACS 2025) - "Two individuals experienced CVF with no resistance testing, switched to boosted darunavir-based regimens, and resuppressed to VL<50 copies/mL. Virologic suppression was consistent across BMI categories. These real-world data support prior studies demonstrating durable effectiveness and tolerability of CAB+RPV/LA."

Clinical • Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease