Vocabria (cabotegravir oral) / ViiV Healthcare, Shionogi - LARVOL DELTA

Differential Effects of Antiretroviral HIV Integrase Inhibitors on Vascular Cell Adhesion Molecules. (PubMed, Antiviral Res) - "Given the role of adhesion molecules in mediating endothelial interactions with leukocytes and platelets during vascular inflammation and thrombosis, we compared the impact of four INSTIs-dolutegravir (DTG), bictegravir (BIC), raltegravir (RAL), and cabotegravir (CAB)-and the non-nucleoside reverse transcriptase inhibitor doravirine (DOR), which is not associated with excessive CV risk, on adhesion molecule expression. Our findings reveal distinct immunomodulatory profiles among the different INSTIs in vitro, rather than a class-wide effect. Future studies in patients with HIV will be needed to confirm the proinflammatory effects of DTG, BIC and CAB and to explore their potential implications for CV risk."

Journal • Cardiovascular • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Thrombosis • ICAM1 • ITGAM • VCAM1

Virological failure with NNRTI resistance on CAB+RPV-LA in a man with subtherapeutic cabotegravir levels (EACS 2025) - No abstract available

Infectious Disease

Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum (clinicaltrials.gov) - P=N/A | N=205 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Two Different Formulations of Long-acting Cabotegravir in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: ViiV Healthcare | Trial primary completion date: Jul 2025 ➔ May 2027

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Discontinuation of Cabotegravir for PrEP: Challenges and Opportunities (IDWeek 2025) - No abstract available

Infectious Disease

Reasons for choosing oral-lead-in versus direct-to-injection when switching to long-acting antiretroviral therapy in East and Southern Africa (IAS-HIV 2025) - P3 | "Product labels for LAI cabotegravir (CAB) and rilpivirine (RPV) in USA and Europe include an optional one-month oral-lead-in (OLI) prior to initiating injections, despite data from high-income settings demostrating the saftey of direct-to-injection (DTI). Preference for OLI versus DTI varied by country. Providing reassurance about safety and tolerability of CAB+RPV could increase DTI preference and simplify implementation in a public health setting."

Human Immunodeficiency Virus • Infectious Disease

Long-acting cabotegravir and rilpivirine in adults with suboptimal HIV control in sub-Saharan Africa: the IMPALA trial 48-week results (IAS-HIV 2025) - P3 | "BACKGROUND: In sub-Saharan Africa, 1.3 million people taking oral antiretroviral therapy (ART) are not virally suppressed. In people with adherence challenges, CAB+RPV-LA was non-inferior to dolutegravir-based ART for viral suppression and CVF, and performed better when considering any VL >1000 copies/ml, which is relevant for HIV transmission risk. A strong preference for injectable therapy, indicates that CAB+RPV-LA may play a key role for specific populations in the public health approach."

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

Therapeutic Drug Monitoring of Long-Acting Cabotegravir and Rilpivirine in a National Cohort of People With Human Immunodeficiency Virus Type 1: First Results From the ANRS-MIE CARLAPOP Study. (PubMed, Clin Infect Dis) - "Our large real-world study confirms significant variability in CAB and RPV exposure, with BMI and sex as key predictors of lower Ctrough. Suboptimal CAB and RPV Ctrough, particularly in people with obesity, increases the risk of VF during the first year of treatment, highlighting the usefulness of TDM in clinical practice."

Journal • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Obesity • CD4

ATLAS-2M: Efficacy, Safety and Tolerability Study of Long-acting Cabotegravir Plus Long-acting Rilpivirine (CAB LA + RPV LA) in Human-immunodeficiency Virus-1 (HIV-1) Infected Adults (clinicaltrials.gov) - P3 | N=1049 | Active, not recruiting | Sponsor: ViiV Healthcare | Trial completion date: Dec 2025 ➔ Dec 2029

Head-to-Head • Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Ultra-long-acting injectable, biodegradable, and removable in-situ forming implant with cabotegravir for HIV prevention. (PubMed, J Control Release) - "The approved long-acting injectable Apretude® is administered every two months and elicits a long pharmacokinetic tail of >15 months that can lead to potential drug-resistant virus [6]. Whole-body X-ray imaging showed that implants were visible for up to 268 days post administration with no noticeable migration. This is the first report of a CAB/BaSO₄ ISFI that is imageable, ultra-long-acting (>180 days), biodegradable, and removable, that can potentially revolutionize current HIV PrEP and help curb the global HIV epidemic."

Journal • Fatigue • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Evaluation of 28-week Antiretroviral Treatment with Albuvirtide and Cabotegravir in HIV Patients with Stable Virologic Suppression: Efficacy, Pharmacokinetics, and Safety (ChiCTR) - P4 | N=10 | Completed | Sponsor: Guangzhou Eighth Peoples Hospital Guangzhou Medical University; Guangzhou Eighth Peoples Hospital Guangzhou Medical University | Not yet recruiting ➔ Completed | Phase classification: PN/A ➔ P4

Phase classification • Trial completion • Human Immunodeficiency Virus • Infectious Disease

Lenacapavir (Yeztugo) for HIV pre-exposure prophylaxis. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Human Immunodeficiency Virus • Infectious Disease

SY19 Pregnancy and long-acting ARVs for prevention and treatment (IAS-HIV 2025) - "This symposium will present new data on lenacapavir and cabotegravir in pregnancy and breastfeeding, outline plans for inclusive research, and discuss priority actions to advance research, development, introduction and use of new long-acting ARVs for HIV prevention and treatment during pregnancy and breastfeeding. It is aimed at research networks, communities, country programme managers, companies, funders, technical partners and regulators."

Human Immunodeficiency Virus • Infectious Disease

A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Two Different Formulations of Long-acting Cabotegravir in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: ViiV Healthcare | Trial completion date: Jul 2025 ➔ May 2027

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Is long-acting injectable antiretroviral therapy safe in countries with high hepatitis B prevalence?: insights from the IMPALA study (IAS-HIV 2025) - P3 | "The WHO recommended first-line HIV regimen (tenofovir disoproxil, lamivudine, dolutegravir, TLD) both prevents and treats hepatitis B disease. Novel long-acting (LA) injectable antiretrovirals including cabotegravir (CAB) and rilpivirine (RPV), are not active against hepatitis B, raising concerns about reactivation in individuals with prior hepatitis B exposure... The high number of hepatitis B-related screen-outs highlights challenges for LA therapy in hepatitis B endemic countries. While hepatitis B reactivation did not occur in individuals with immunity (HepBsAb >10 IU), the risk of de novo infection remains in those receiving CAB+RPV LA without immunity. This demonstrates the need for strengthened vaccination efforts, particularly among those switching to CAB+RPV LA."

Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

The Meandrous Route of Rilpivirine in the Search for the Miraculous Drug to Treat HIV Infections. (PubMed, Viruses) - "For this purpose, it was subsequently combined with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), darunavir (boosted with ritonavir or cobicistat) or dolutegravir. Its wide-spread use is thanks to its combination with cabotegravir (CAB) in the form of a long-acting intramuscular injection once per month (QM), later twice per month (Q2M), for the treatment of adults, later extended to adolescents and pregnant women, with HIV infections. The long-acting CAB plus RPV should not be administered in patients treated with rifampicin or rifabutin, patients with virological failure or patients with resistance to CAB or RPV, or patients with hepatitis B virus (HBV) infection. Long-acting CAB+RPV may lead to pain at the site of injection which would diminish over time."

Journal • Review • Hepatitis B • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Pain

Cerebrospinal fluid concentrations, viral suppression and biomarkers with long-acting cabotegravir and rilpivirine intramuscular injections. (PubMed, Antiviral Res) - "The combination of LA CAB/RPV can achieve therapeutic CSF concentrations throughout the dosing intervals and may suppress HIV replication in the CNS. No significant changes in CSF biomarkers of inflammation or neuronal injury were observed, indicating a neutral CNS effect."

Biomarker • Journal • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CSF NfL

Pregnancy and neonatal outcomes following prenatal exposure to cabotegravir (CAB): data from The Antiretroviral Pregnancy Registry (APR) (IAS-HIV 2025) - "BACKGROUND: Cabotegravir (CAB) is indicated for the treatment of HIV-1 infection in combination with rilpivirine and as a single agent for prevention of HIV. While no significant safety concerns were seen, definitive conclusions on the safety of CAB use in pregnancy cannot be drawn due to a limited number of pregnancies reported and the data should be interpreted with caution. Providers are encouraged to register ARV exposed pregnancies, especially those exposed to newer ARVs such as CAB, at APR (apregistry.com). ?"

Human Immunodeficiency Virus • Infectious Disease

High virologic suppression and few virologic failures with Long-Acting Cabotegravir + Rilpivirine in Treatment Experienced Virologically Suppressed Individuals from COMBINE-2 cohort in Europe (IAS-HIV 2025) - "This real-world data on PWH virologically suppressed at initiation on CAB+RPV LA in Europe demonstrated high levels of virologic control with low CVF. These data demonstrate high levels of adherence and persistence to the regimen. Among few with CVF, suppression was achieved after switching to PI or INI-based regimen."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Navigating choices: anticipated drawbacks to PrEP modalities among sexual and gender diverse adolescents in Brazil (IAS-HIV 2025) - "We aimed to analyze anticipated drawbacks to choosing (LAI-PrEP) and event-driven PrEP (ED-PrEP) among sexual and gender diverse adolescents in Brazil. The PrEP15-19 Choice´s implementation study offered oral PrEP (daily and ED-PrEP) and LAI-PrEP using cabotegravir as a choice to cisgender men who have sex with men (MSM), transgender and non-binary (NB) people aged 15 to 19 in three Brazilian cities... Anticipated drawbacks can play a critical role in adolescents´ decisions to initiate PrEP. Addressing these concerns is vital to reduce barriers and tailor PrEP interventions to the diverse needs of adolescent subgroups."

Pain

Indirect treatment comparison of the efficacy of cabotegravir and lenacapavir for HIV pre-exposure prophylaxis (PrEP) versus no PrEP (IAS-HIV 2025) - "CAB and LEN both offer high and similar efficacy in reducing HIV acquisition risk compared with No PrEP and this was generally consistent when using oral PrEP as a common comparator with adjustment for differences in adherence (data not shown here). Additional factors associated with these regimens, including the potential for drug-drug interactions and adverse events (eg, injection site reactions), real-world usage, seroconversion resistance, and patient preference, will be important to comprehensively assess clinical value and assist with decision-making."

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

Community priorities for PrEP research and delivery: insights from the People's Research Agenda (IAS-HIV 2025) - "Innovations like injectable options, including cabotegravir (CAB) and lenacapavir (LEN), have transformed HIV prevention by offering diverse delivery mechanisms, protection durations, and adding choice. Communities play an important role in shaping HIV prevention R&D and delivery. The PRA provides a clear roadmap for aligning innovations with community-defined needs and preferences. In 2025, the PRA will focus on developing a framework for advocacy, decision-making and accountability to address critical gaps in HIV prevention research and delivery."

Human Immunodeficiency Virus • Infectious Disease

Capsid inhibition with lenacapavir in HIV-1 infection: real-life results from the French compassionate use program (IAS-HIV 2025) - "OBR included mainly darunavir/r (n=13), dolutegravir (n=11), cabotegravir (n=10), fostemsavir (n=12), maraviroc (n=8), ibalizumab (n=7) and enfuvirtide (n=4). In this real-life cohort of highly treatment-experienced HIV-1 participants, lenacapavir in combination with an OBR resulted in a high level of virological suppression up to 26 weeks, even increasing throughout the end of follow-up."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4

Lenacapavir plus Cabotegravir real-world use cases from the National Clinician Consultation Center (IAS-HIV 2025) - "In this case series of 10 PWH with virologic failure on oral ART, LEN+CAB+/-RPV was highly effective in achieving viral suppression. The most common reason for modification was detectable viral load on oral ART. These data and other case series of LEN+CAB support further research on LEN+CAB+/-RPV among PWH who are unable to adhere to oral ART or have a drug-resistant virus."

Clinical • Real-world • Real-world evidence • Human Immunodeficiency Virus • Infectious Disease

Novel approach for the simultaneous prevention of HIV and Mtb infection (IAS-HIV 2025) - "Here, we evaluated the pharmacokinetics (PK) of an LA cabotegravir (CAB) formulation co-administered with an LA rifabutin (RFB) formulation. BALB/c mice received a subcutaneous injection of either 1) LA RFB [mean RFB concentration: 1,205 mg/kg] (n=5), 2) LA CAB [mean CAB concentration: 461 mg/kg] (n=5), or 3) two injections – one injection of LA RFB [mean RFB concentration: 1129 mg/kg], and one injection of LA CAB [mean CAB concentration: 489 mg/kg] (n=5). Co-administration of LA RFB and LA CAB does not alter the individual drug concentrations in serum. Additionally, administration of RFB did not result in lower levels of CAB in tissues. Rather in animals that also received LA RFB, we found higher concentrations of CAB in lung, kidney, and brain."

Human Immunodeficiency Virus • Infectious Disease • Respiratory Diseases • Tuberculosis