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

Perspectives of Horizon Scanning Tool Introduction to HTA in Ukraine: Identifying HIV Technologies (ISPOR 2025) - "Six new health technologies for Ukraine were prioritized: cabotegravir (an alternative to tablet-based regimens for daily pre-exposure prophylaxis), ibalizumab (for the treatment of multidrug-resistant HIV), the dapivirine vaginal ring (to reduce the risk of HIV infection), the Harmony Portable Nucleoside Analog Analyzer, a Machine Learning Model-based Tool for identifying patients at risk of discontinuing HIV treatment, and an SMS Notification Service for HIV-positive individuals. The case study demonstrated that the horizon scanning tool can serve as an effective method for informing the Ukrainian healthcare system about new HIV/AIDS technologies. This tool is perspective to be integrated as one of the stages in the HTA process, specifically for the early HTA stage."

Human Immunodeficiency Virus • Infectious Disease

Cost-Effectiveness Analysis of Lenacapavir Compared to Cabotegravir and Generic Oral FTC/TDF for HIV Pre-Exposure Prophylaxis for Cis-Gender Women in the United States (ISPOR 2025) - "LEN is not cost-effective compared to generic FTC/TDF or CAB-LAI for HIV PrEP. However, LEN offers a viable alternative with reduced administration frequency for individuals at risk of acquiring HIV infection."

Clinical • Cost effectiveness • HEOR • Human Immunodeficiency Virus • Infectious Disease

HIV susceptibility to second-generation integrase strand transfer inhibitors among people with multidrug resistance: a systematic review and meta-analysis protocol. (PubMed, Ther Adv Infect Dis) - "We will include studies of adults and/or children exposed to dolutegravir, bictegravir, or cabotegravir following treatment failure to more than one drug class. The results will, therefore, contribute to set up baseline data for optimal management of people living with HIV harboring multidrug-resistant viruses. PROSPERO: CRD42023470922."

Journal • Retrospective data • Human Immunodeficiency Virus • Infectious Disease

A review of pharmacokinetic data describing long-acting injectable cabotegravir during pregnancy. (PubMed, Expert Opin Pharmacother) - "For treatment, CAB-LA is currently approved in combination with long-acting rilpivirine (RPV-LA). Other long-acting prevention and treatment strategies are in development. Future studies assessing long-acting strategies are necessary during drug development to ensure equitable and timely access to novel therapies for all individuals."

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

Matrix Approach Assessment of Cabotegravir Drug-Drug Interactions with OAT1/OAT3 Substrates and UGT1A1/UGT1A9 Inhibitors Using Physiologically-Based Pharmacokinetic Modeling. (PubMed, Pharmaceutics) - " PBPK modelling indicated that clinically relevant DDIs are not anticipated with OAT1/3 substrates or UGT1A1/1A9 inhibitors and CAB. With maximal exposure of the LA formulation of CAB being lower than the oral, the results of these simulations can be extrapolated to LA injectable dosing."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • UGT1A1

The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE (clinicaltrials.gov) - P3 | N=456 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=310 ➔ 456

Enrollment change • Human Immunodeficiency Virus • Infectious Disease

Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum (clinicaltrials.gov) - P=N/A | N=205 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting | N=325 ➔ 205

Enrollment change • Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

High Preference for Injectable Pre-exposure Prophylaxis among Young Women in Kenya. (PubMed, AIDS Behav) - "Among previous oral PrEP users, 82% preferred injectable PrEP, 16% preferred oral PrEP, and only 2% preferred the dapivirine vaginal ring...Reproductive-age women in Kenya have a strong interest in long-acting injectable PrEP. Product rollout and implementation needs to consider women's preference and devise best approaches to deliver injectable PrEP."

Journal • Human Immunodeficiency Virus • Infectious Disease • Long-acting Reversible Contraceptives

Despite Increasing Use of INIs to Treat HIV Infection, Resistance to This Class Remains Stable (CROI 2025) - "The integrase inhibitor (INI) class has benefited from many developments: first raltegravir (RAL) and elvitegravir (EVG), followed by dolutegravir (DTG), cabotegravir (CAB) and bictegravir (BIC). The very high level of INI resistance at the beginning of INI use was probably due to the use of RAL in combination with other ARVs that were not fully sensitive during the first 3 years. The INIs used today have a higher genetic barrier that limits the emergence of resistance mutations."

Human Immunodeficiency Virus • Infectious Disease

In Vitro Resistance Profile for GS-1720, a Potent Once-Weekly Oral InSTI in Clinical Development (CROI 2025) - "Results GS-1720 retained potent antiviral activity, defined as an EC50 fold-change (FC) 300, 140 and 119 days in culture, respectively...In a fixed-dose viral breakthrough assay, clinically relevant concentrations of GS-1720 or BIC prevented viral breakthrough while EVG and raltegravir, when tested at their equivalent clinical trough plasma concentrations, showed breakthrough with resistance in 45% and 18% of PBMC cultures (n=44-48/condition), respectively. Conclusions GS-1720 exhibits an in vitro resistance profile comparable to the best-in-class INSTI bictegravir, including high barrier to resistance and minimal cross-resistance within the INSTI class. These observations support the ongoing clinical development of GS-1720 as a novel once-weekly oral INSTI."

Preclinical • Human Immunodeficiency Virus • Infectious Disease

Injectable Cabotegravir PrEP Discontinuations at a Peer Specialist-Led Program in Washington, DC (CROI 2025) - "Peer specialists fostered continued PrEP use among those who discontinued CAB and potentially reduced discontinuations in populations which have a higher risk for HIV. Insurance coverage gaps continue to undermine CAB implementation efforts."

Human Immunodeficiency Virus • Infectious Disease

Early PEPFAR Implementation of Cabotegravir-LA and Implications for Long-Acting HIV Prevention (CROI 2025) - "Background Despite the availability of oral HIV pre-exposure prophylaxis (PrEP), gaps remain in reaching the UNAIDS target of 21.2 million people on PrEP by the end of 2025 and reducing HIV incidence. Lessons learned from early CAB-LA introduction will inform continued scale-up of CAB-LA in additional PEPFAR-supported countries in 2025, with plans to reach 100,000 clients by the end of the year. This platform will also support future HIV prevention products including Lenacapavir."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

Long-Acting Injectable CAB/MPA MPT Implant for Prevention of HIV and Unintended Pregnancy (CROI 2025) - "We evaluated a long-acting (LA), injectable in-situ forming implant (ISFI) as a multi-purpose prevention technology (MPT) to co-formulate cabotegravir (CAB) and medroxyprogesterone acetate (MPA) with the incorporation of a contrast agent for in vivo visualization and ease of retrievability...Our findings showed the ability to visualize the implants with no evidence of implant migration. CAB and MPA elicited undetectable plasma concentration after implant removal highlighting the potential for a discrete and reversible MPT option for adolescent girls and women."

Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Systemic Inflammatory Response Syndrome

"I Like It but I Can't Be the First": Sex Workers' Preferences for LAI PrEP Delivery in South Africa (CROI 2025) - "Decentralized delivery via mobile van was generally preferred over drop-in-centers and clinics to support adherence to LAI-PrEP; however, FSW in eThekwini remained concerned about potential missed injections given frequent travel home, including away from South Africa Conclusions Nearly two years after Cabotegravir received regulatory approval in South Africa, FSW remain largely unable to access LAI-PrEP, despite established efficacy and community interest. As LAI-PrEP products become increasingly available, strategies supporting counseling, education, and diversity in PrEP delivery sites for FSW can optimize implementation and equitable LAI-PrEP uptake and continuation."

Human Immunodeficiency Virus • Infectious Disease • Long-acting Reversible Contraceptives

Association of Trough Concentrations of Cabotegravir and Rilpivirine and HIV-1 RNA (CROI 2025) - "Background The relevance of plasma (trough) concentrations of cabotegravir (CAB) and rilpivirine (RPV) with regard to sustained virologic suppression in people with HIV (PWH) on long-acting treatment (LA) is an ongoing matter of debate. It is unclear if this is also predictive of virologic failure. Based on our findings, however, it warrants further investigation if dosing can be indivualized taking trough concentrations into account."

Human Immunodeficiency Virus • Infectious Disease

Diagnosis, Resistance, and ART Outcomes After HIV Acquisition on CAB-LA PrEP in Routine Care in US (CROI 2025) - "Background Reports of HIV acquisition among persons on cabotegravir (CAB) PrEP are rare thus far in routine clinical care but have occurred...All started DRV-based ART (3 later switched to INSTI-based ART) and all achieved viral suppression to date. Longer-term follow-up is needed to assess the clinical significance of low-frequency INSTI RAMs detected by sensitive assays, and the durability of viral suppression on INSTI-based ART after HIV infection on CAB PrEP."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

In Vitro Modulation of Adipocyte Differentiation by TAF/TDF After Challenge With New ARV Regimens (CROI 2025) - "Background We previously demonstrated in a 3T3L1cells in vitro model of adipogenesis, that Integrase Strand Transfer Inhibitors (INSTI) increase adipogenesis, while, tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF), displayed an inhibitory effect, counteracting increased adipogenesis caused by INSTIs [dolutegravir (DTG), bictegravir (BIC)]...Methods We used a 3T3-L1 cells in vitro model of adipogenesis to study the effects on adipocyte differentiation of the NNRTIs doravirine (DOR) and rilpivirine (RPV), alone or in combination with the previously evaluated DTG and the newer INSTI cabotegravir (CAB), or TDF or TAF...Furthermore, NNRTIs and CAB enhanced the expression levels of ER-TR7 compared to control, being the combination DTG+DOR less effective in this activity. Conclusions Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs and NNRTIs is able to increase adipocytic differentiation and to drive a number of..."

Preclinical • Diabetes • Diabetic Nephropathy • Metabolic Disorders

HIV-1 Drug Resistance Trends in the Era of Modern Antiretrovirals: 2018-2024 (CROI 2025) - "Doravirine and rilpivirine DRMs remained low, with respective 2024 prevalences of 2% (RNA) and 2.9% (DNA) and 6.3% (RNA) and 10.1% (DNA)...Cabotegravir DRM prevalence in 2024 was 3.8% (RNA) and 2.5% (DNA)...Conclusions Prevalence of NRTI and NNRTI resistance declined which is consistent with increased use of regimens with higher resistance barriers, improved tolerability, and more convenient dosing, resulting in better adherence. Prevalence of INSTI DRMs was low, supporting US guidelines for limiting INSTI resistance testing to cases of treatment failure, suspected transmitted resistance, or infection during INSTI-based PrEP."

Human Immunodeficiency Virus • Infectious Disease

High Incidence of Curable Sexually Transmitted Infections in HPTN 084: A Tertiary Analysis (CROI 2025) - "Cabotegravir (CAB) PrEP efficacy in the blinded study period was compared for people with and without STIs using Cox regression...There was no difference in CAB efficacy between women who had STIs (hazard ratio, HR, 0.08 95% CI 0.02-0.34) vs those who did not (HR 0.15 95% CI 0.03-0.64, p=0.58). Conclusions Curable STI prevalence, incidence and recurrence was high in this cohort of women accessing PrEP, highlighting the urgent need to prioritize investments in novel, multipurpose, and scalable interventions to prevent STIs and HIV among these women and their partners."

Human Immunodeficiency Virus • Infectious Disease

Outcomes on Cabotegravir + Rilpivirine in Suppressed People With HIV (PWH) in TRIO Health US Cohort (CROI 2025) - "CVF with emergent INSTI resistance was rare. These results are consistent with previous studies reporting low rates of emergent INSTI resistance and higher rates of NNRTI resistance among failures."

Human Immunodeficiency Virus • Infectious Disease

Can "Equivalence" of a Generic Cabotegravir LA Be Inferred From a Shortened Pharmacokinetic Study? (CROI 2025) - "Despite this low bar, truncation of the profiles to below 10 weeks for 800mg fittings was unable to accurately predict parameters determined from the full profile. The analysis sheds light on the complexity of the challenge and may be useful to inform further development of strategies for accelerated "equivalence" evaluation for generic LAI."

PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Structural and Mechanistic Insights Into Cabotegravir Resistance in HIV-1 Integrase (CROI 2025) - "The mutations cause rearrangements in the active site that reduce the binding of CAB and, by extension, other INSTIs. Conclusions Our combined virology, structural biology, and molecular dynamics analyses provides a detailed mechanistic understanding of CAB/INSTI resistance, yielding a foundation for the development of next-generation INSTIs capable of overcoming problematic complex resistant IN variants."

Human Immunodeficiency Virus • Infectious Disease

PILLAR Month 12 Clinical Results: Zero HIV Acquisition and High Persistence With CAB LA for PrEP (CROI 2025) - P4 | "Long-acting (LA) cabotegravir (CAB) administered every 2 months via intramuscular injection is the first and only approved LA medication for HIV-1 pre-exposure prophylaxis (PrEP)...Conclusions These real-world data obtained from a diverse population support CAB LA as an effective PrEP option associated with high persistence. No cases of HIV acquisition were observed through 12 months irrespective of the testing method(s) used, potentially suggesting a less prescriptive testing guideline."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Pain

Dynamic Choice HIV Prevention With Cabotegravir (CAB-LA): A Model-Based Cost-Effectiveness Analysis (CROI 2025) - "DCP with Cab-LA incurs the lowest mean net DALYs (-7700 per year over 50 years; ICER compared with status quo = $389), and is the cost-effective policy. Conclusions Offering structured PrEP/PEP choice, including Cab-LA, could reduce HIV incidence by one-third over 10 years and is likely cost-effective across settings in east and southern Africa."

Cost effectiveness • HEOR • Human Immunodeficiency Virus • Infectious Disease

An Injectable Multipurpose Implant With CAB and MPA for Long-Acting HIV Prevention and Contraception (CROI 2025) - "We recently demonstrated in-situ forming implants (ISFIs) in macaques can deliver cabotegravir (CAB) above protective benchmarks (>4 PA-IC90) for more than 5 months...Our findings showing a lack of implant migration are reassuring and suggest a limited value of adding BaSO4, particularly given the reduction in CAB release. Long-term suppression of ovulation after implantation and rapid reversal following removal suggest ISFIs may provide a discrete and flexible MPT option for adolescent girls and women."

Human Immunodeficiency Virus • Infectious Disease • Long-acting Reversible Contraceptives • Women's Health