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

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

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

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

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

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

Diagnostic outcomes among women with detectable HIV RNA after starting injectable cabotegravir within a multi-method PrEP market implementation study (IAS-HIV 2025) - "In four cases of detectable HIV RNA at CAB PrEP initiation with follow-up test results, two continued CAB PrEP and two were referred for ART, indicating that RNA results did not clarify HIV status for individuals starting CAB PrEP. The utility of HIV RNA in HIV testing algorithms for PrEP initiation/ continuation should be further evaluated in programmatic settings."

Clinical • 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

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

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

Infectious Disease

Phase 2 Trial of Long-Acting Cabotegravir and VRC07-523LS for Viral Suppression in Adults with HIV-1: ACTG A5357. (PubMed, Clin Infect Dis) - "The VRC07-523LS plus CAB-LA regimen maintained viral suppression in 93% of participants, with only transient infusion reactions observed; however, instances of virologic breakthrough suggest that future studies should focus on optimizing efficacy outcomes. These results support continued investigation of bNAb-based long-acting ART combinations."

Journal • P2 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Fetal Defects in Mice Treated with Integrase Strand Transfer Inhibitors: Comparison of Dolutegravir, Raltegravir, Bictegravir and Cabotegravir. (PubMed, J Infect Dis) - "While INSTIs represent a critical advance in the management of HIV infection, the findings of this study demonstrate a link between INSTI therapy and adverse fetal outcomes. This highlights the need for continued surveillance of pregnancy outcomes in women exposed to INSTIs."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Lessons for long-acting lenacapavir: catalysing equitable PrEP access in low-income and middle-income countries. (PubMed, Lancet HIV) - "Despite substantial advances in biomedical HIV prevention, including long-acting injectable pre-exposure prophylaxis (PrEP) options such as cabotegravir, barriers to widespread adoption and scale-up persist in low-income and middle-income countries. Without deliberate policy, programmatic, and financing interventions, new prevention technologies risk following slow adoption patterns of previous innovations, weakening a needed transformation of the HIV response. Drawing on lessons from the scale-up of antiretroviral therapy, and experience with previous biomedical prevention tools, a new ten-point framework should be adopted to accelerate individual and epidemiological impact-even at this time of extraordinary uncertainty."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease

Strategies to Manage Dosing Deviations and Interruptions of Cabotegravir Long-Acting Intramuscular Injections. (PubMed, Clin Pharmacol Drug Dev) - "Recommended strategies include no action for higher-than-planned doses, corrective dosing for lower-than-planned doses, strict adherence to schedule, reinitiating the loading dose after delays >1 month, and oral bridging. These findings were incorporated into product labeling and can inform next-generation cabotegravir and other long-acting agent development."

Journal • Human Immunodeficiency Virus • Infectious Disease

Long-Term Real-World Use of Cabotegravir/Rilpivirine: Adherence and Virological Efficacy over a 44-Month Observation Period. (PubMed, Infect Dis Ther) - "This real-world study, with a 44-month observation period and follow-up of up to 10 years on LA-CAB/RPV, confirms its long-term efficacy and safety, supporting its durability as a maintenance option for PLWH, even with occasional delays and slightly lower adherence than seen in clinical trials, and additionally underscores the importance of individualized care and structured monitoring in real-world settings."

Journal • Real-world evidence • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease • Psychiatry

Indirect Treatment Comparison of Long-Acting Injectable Cabotegravir as Pre-exposure Prophylaxis When Compared with no Pre-exposure Prophylaxis for HIV Prevention. (PubMed, Infect Dis Ther) - "The ITC of cabotegravir versus no PrEP predicted similar estimates of cabotegravir effectiveness in the HPTN 083 and 084 trials, suggesting a very high level of efficacy despite differences in population, setting, underlying rate of HIV acquisition, and oral TDF/FTC adherence. These estimates support the generalizability of the cabotegravir results from both HPTN trials to other populations and regions than those in which these trials were conducted. Graphical abstract available for this article."

Journal • Human Immunodeficiency Virus • Infectious Disease

Trough concentrations of cabotegravir and rilpivirine and their association with detectable viral load in people with HIV on long-acting treatment. (PubMed, Infection) - "Lower CAB and RPV concentrations were associated with viremia, particularly using the ROC-derived thresholds. Among individuals with VF and available drug concentration data, 87.5% had at least one drug below these thresholds. Further research on therapeutic drug monitoring is warranted."

Journal • Human Immunodeficiency Virus • Infectious Disease

Patient-reported outcomes in clinical trials assessing the effectiveness of cabotegravir + rilpivirine long-acting injections as antiretroviral therapy: A systematic review. (PubMed, HIV Med) - "This review underscores the potential of CAB + RPV-LA in improving patient adherence and satisfaction while offering insights for future studies on longer-term outcomes of LAI use."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease