Fuzeon (enfuvirtide) / Roche - LARVOL DELTA

Insulin-derived nodular amyloidosis at sites of injection. (PubMed, Proc (Bayl Univ Med Cent)) - "Insulin, along with enfuvirtide, is one of two known medications capable of causing iatrogenic nodular amyloidosis, and patients should avoid repeat insulin injections into sites of amyloidosis, as absorption of insulin may be altered in these areas. Accurate amyloid typing may obviate the need for systemic evaluation and prevent accompanying costs and morbidity."

Journal • Amyloidosis • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

HDAd vector-mediated in vivo HSPC engineering to express HIV fusion inhibitors imparts HIV resistance in humanized mice. (ASGCT 2026) - "Methods We generated helper-dependent adenovirus HDAd6/3 vectors expressing HIV-FIs including i) a de-immunized C46-v20, ii) a stability-enhanced C34 (Sifuvirtide, C34-SFT), and iii) the FDA- approved Enfuvirtide (T20) using various promoters (human β-actin and human ubiquitin-C for ubiquitous expression, CD68s for myeloid expression, PVT for erythroid expression)...Six weeks after humanization, HSPCs were mobilized using G-CSF and AMD3100, followed by cytokine prophylaxis and intravenous administration of an HDAd6/3 vector encoding the secreted form of C46-v20, together with HDAd6/3.SB100x vector to enable transgene integration...Conclusion The central result of this study is the demonstration that C46v20 mediates robust protection against HIV replication after in vivo HSC transduction that results in constitutive expression of the HIV-FI in humanized mice. Future studies will leverage the full cargo capacity of HDAd vectors, which can accommodate transgenes of up to..."

Preclinical • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation • CD34 • CXCR4 • MGMT • MIR126 • UBC

FAERS DATABASE ANALYSIS REVEALS ANENCEPHALY ASSOCIATED WITH ANTIRETROVIRAL DRUG EXPOSURE (ISPOR 2026) - "Emtricitabine had the highest number of reports (n=51), followed by Ritonavir (n=32) and Tenofovir (n=28)...Tipranavir showed the strongest signal (551.688; 343.42-886.26), followed by Etravirine (97.723; 50.453-189.28) and Enfuvirtide (97.684; 48.489-196.789). Among FDCs, Lamivudine and Zidovudine (87.799; 50.529-152.56) had the highest signal... This study highlights a potential safety concern regarding the association between antiretroviral agents and anencephaly. Continued pharmacovigilance and targeted epidemiological studies are warranted to further investigate and mitigate these risks in vulnerable populations."

CNS Disorders

Development of a triplex FMCA assay for genotyping three genes, ADH1B, ADH1C, and ALDH2, involved in alcohol metabolism. (PubMed, Sci Rep) - "Three functional single nucleotide variants (SNVs)‒ALDH2 rs671 (p.E504K), ADH1C rs698 (p.I350V), and ADH1B rs1229984 (p.R48H)‒are key genetic determinants of human alcohol metabolism...In conclusion, this triplex FMCA assay provides a rapid, cost-effective, and streamlined method for the simultaneous genotyping of ADH1B, ADH1C, and ALDH2. Given its high accuracy and ease of implementation, this method serves as a practical alternative to conventional sequencing, positioning it as a valuable tool for both large-scale epidemiological research and routine clinical assessment of alcohol-related health risks."

Journal • Esophageal Cancer • Gastric Cancer • Hepatology • Oncology • Solid Tumor • ADH1B • ADH1C • ALDH2

Design of Artificial Peptide Against HIV-1 Based on the Heptad-Repeat Rules and Membrane-Anchor Strategies. (PubMed, Pharmaceuticals (Basel)) - "Current peptide inhibitors like Enfuvirtide suffer from drug resistance and short in vivo half-life...EK35S-Palm demonstrates superior efficacy and stability over current therapies. These approaches hold great potential for overcoming the current therapy limitations and advancing the more effective and durable HIV-1 fusion inhibitors."

Journal • Human Immunodeficiency Virus • Infectious Disease

Disproportionality Analysis Of Vedolizumab to Identify a Putative Signal Using Real-World Postmarketing Surveillance Data Reported in the FAERS Database (ISPOR-EU 2025) - "OBJECTIVES: The study aimed to identify the novel signals of enfuvirtide reported within the USFDA Adverse Event Reporting System (FAERS) database An in-depth case/non-case retrospective disproportionality analysis was conducted in the publicly available FAERS database for Vedolizumab. This study revealed novel risk signal and important insights on Vedolizumabassociated Bell's Palsy. The authors conclude that the health care practitioners should monitor for the occurrence of Bell's Palsy among patients. The epidemiological studies should be conducted to validate the putative signal in real-world scenarios among the patients administered with Vedolizumab to improve patient safety."

Clinical • P4 data • Real-world • Real-world evidence • CNS Disorders • ROR1

HIV-1 Entry Mechanisms: Protein-Host Receptor Interactions and Membrane Fusion Dynamics. (PubMed, Front Biosci (Landmark Ed)) - "Fusion peptide insertion, six-helix bundle formation, and membrane merger are critical targets for inhibitors like T20 (enfuvirtide)...We highlight strategies to disrupt Env-receptor interactions, block fusion intermediates, and harness cross-viral principles to counteract drug resistance and refine vaccine approaches. These insights not only deepen our understanding of HIV-1 pathogenesis but also drive the innovation of novel antiviral strategies."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • CD4 • CXCR4

Comparative Performance of iSeq 100 and MiSeq i100 for Pooled Sequencing of HIV, HCV, TB, and 16S rRNA (AMP 2025) - "Both sequenced HIV capsid and envelope, enabling detection of mutations related to new treatments (e.g., enfuvirtide, fostemsavir, lenacapavir). Both platforms are suitable for high-throughput sequencing of pooled HIV, HCV, TB, and 16S rRNA samples. MiSeq i100 offers superior sensitivity, depth, and speed, making it well suited for research and diagnostics. iSeq 100 remains a cost-effective tool for routine diagnostics."

Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Respiratory Diseases • Tuberculosis

Next-Generation Antiviral Peptides: AI-Driven Design, Translational Delivery Platforms, and Future Therapeutic Directions. (PubMed, Virus Res) - "Translational aspects are addressed by discussing novel delivery systems such as nanoparticles, hydrogels, and intranasal/inhalable formulations, as well as clinical trial examples (like, enfuvirtide (T-20), sifuvirtide, lactoferrin-based formulations, PAC-113). Finally, we explore future directions, including CRISPR- and mRNA-based peptide delivery and synergies with immune checkpoint inhibitors. By combining classical mechanisms with AI-driven design and innovative delivery platforms, this review underscores the potential of AVPs as versatile antiviral agents ready for clinical translation."

Journal • Review • Oncology

Harnessing Antiviral Peptides: From Molecular Mechanisms to Clinical Translation. (PubMed, Curr Res Pharmacol Drug Discov) - "Both natural and synthetic AVPs are discussed, including FDA-approved agents such as enfuvirtide (HIV) and boceprevir (HCV), along with candidates currently in clinical trials. AVPs represent a promising class of antiviral agents with the potential to address current therapeutic gaps and improve future outbreak response. This review highlights their growing importance in the field of antiviral therapy and outlines future directions for research and development."

Journal • Review • 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

Novel haplotypes of genetic polymorphisms in alcohol metabolizing enzymes in Kampala, Uganda. (PubMed, BMC Res Notes) - "Five SNPs: ADH1B (rs1229984 and rs2066702), ADH1C (rs1693482 and rs698) and ALDH2 (rs671) were analyzed by PCR-restriction fragment length polymorphism assays in 250 samples...Notably ADH1B*1-ADH1C* new, had the second highest frequency (25.2%). Our study provides the first data on novelADH1B-ADH1C haplotypes in alcohol metabolizing genes in the Ugandan population."

Journal • ADH1B • ADH1C • ALDH2

Utilizing Machine Learning to Improve Neutralization Potency of an HIV-1 Antibody Targeting the gp41 N-Heptad Repeat. (PubMed, ACS Chem Biol) - "However, despite the potency of NHR-targeting peptides and clinical efficacy of the NHR-targeting entry inhibitor enfuvirtide, no potently neutralizing NHR-directed monoclonal antibodies (mAbs) nor antisera have been identified or elicited to date...We identify a variant with 5-fold improved neutralization potency, D5_FI, which is the most potent NHR-directed monoclonal antibody characterized to date and exhibits broad neutralization of tier-2 and -3 pseudoviruses as well as replicating R5 and X4 challenge strains. Additionally, our work highlights the ability of protein language models to efficiently identify improved mAb variants from relatively small libraries."

Journal • Human Immunodeficiency Virus • Infectious Disease

Transdermal delivery of enfuvirtide using dissolving microneedles integrated with novel insertion and removal indicator. (PubMed, J Control Release) - "These findings underscore DMAPs as a promising alternative to subcutaneous injection of enfuvirtide, capable of reducing ISRs and potentially enhancing patient adherence. Notably, this work introduced an innovative solution for prompt patch removal upon complete drug delivery, effectively addressing dosing inconsistencies and enabling individualised administration, which is crucial for ensuring the reliability and patient acceptability for widespread adoption of this technology."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pain

In vivo Engineering of HSPCs for HIV Gene Therapy using Helper-Dependent Adenoviral Vectors expressing HIV Fusion Inhibitors (ASGCT 2025) - "To test this, we are evaluating three fusion inhibitors expressed from two promoters (human β-Actin and human ubiquitin-C): i) de-immunized C46-v20, ii) stability-enhanced C34 (Sifuvirtide, C34-SFT), and iii) FDA-approved Enfuvirtide (T20)...To assess its safety, we performed in vivo HSPC transduction in GCSF/AMD3100-mobilized human CD46 transgenic mice...The administration of dexamethasone, MMF, and rapamycin rescued the remaining mice, suggesting inflammatory responses by/to C46-v20...We believe that this strategy will improve the safety and efficacy of HIV therapy. Disease Focus of Abstract:HIV"

Gene therapy • Preclinical • Viral vector • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Targeted Protein Degradation • CD34 • CD46 • HMGA2 • MIR126 • UBC

Research strategies of the N-peptide fusion inhibitor: a promising direction for discovering novel antivirals. (PubMed, J Virol) - "N-peptide fusion inhibitors, whose sequences are different from enfuvirtide, exhibit potential anti-HIV-1 activity and inhibition of drug-resistant strains through the advanced coiled-coil conformation and are expected to serve as novel peptide inhibitors in the iteration of enfuvirtide. This paper provides a comprehensive summary of N-peptide fusion inhibitor research and development (R&D) to date, with the aim of providing investigators with prospective ideas for exploring antivirals."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease

Quality by Design-Guided Development of Hydrogel-Forming Microneedles for Transdermal Delivery of Enfuvirtide. (PubMed, ACS Appl Mater Interfaces) - "Ex vivo permeation studies elucidated the sustained and controlled release kinetics of enfuvirtide via MNs fabricated from the optimized formulation, attaining a maximum permeation of 36.26% using 11 × 11 molds, compared to 28.45% permeation observed with the control system over 24 h. Furthermore, the system's favorable swelling kinetics and enhanced viscoelastic properties significantly augmented its delivery performance relative to conventional approaches. This study not only establishes hydrogel-forming MNs as an innovative and efficacious delivery platform for enfuvirtide but also presents a robust, systematic methodology for MN development, offering transformative potential for broader pharmaceutical applications and therapeutic paradigms."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pain

The economic impacts of marine plastic debris in South Africa: A preliminary estimate. (PubMed, Mar Pollut Bull) - "The cost per tonne of plastic (per year) ranges between R70 635 and R698 186 (mid-range estimate of R282 028 per tonne)...The plastic entering South Africa's marine environment each year imposes a total cost of between R169 billion and R1.69 trillion (mid-range estimate = R677 billion) in terms of impacts on ecosystem services over its lifetime. However, there is a need for further research to assess the full set of environmental, social and economic costs and benefits of plastics, of alternatives to plastic, and of various types of intervention strategies; to inform the most suitable strategies for reducing the leakage of plastic waste to the environment."

HEOR • Journal

Investigating the combination of Temsavir and entry inhibitors on HIV replication: Synergistic and antagonistic effects observed against various R5-tropic envelopes. (PubMed, Virology) - "Here, we investigated the effects of combining Temsavir with other HIV entry inhibitors, including CD4 mimetic BNM-III-170, T20 or enfuvirtide, Ibalizumab, and Maraviroc. These results are promising for the potential of co-administrating antiretrovirals for HIV treatment and highlights the importance of developing advanced antiviral strategies. On the other hand, the variable responses against different R5-tropic envelopes underscore the complexity of designing universally effective combination antiviral therapies."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Treatment Cost of Heavily Treatment-Experienced Adult Patients With Multi-Drug Resistant HIV-1 Infection in Brazil (ISPOR-EU 2024) - " The total cost of a patient is BRL 100,528, 77% of which is related to ART regimens, with maraviroc and enfuvirtide representing the costly treatments and being included in 19% and 10% of optimized background therapy (OBT) regimens, respectively. Patients with lower CD4+ cell counts require a higher level of healthcare resources with the potential to overload the system with higher costs for treatment and disease control. New technologies aimed at controlling the progression of HIV-1 and CD4+ cell counts can contribute to better quality of life and reduced healthcare resource utilization by the Sistema Único de Saúde (SUS)."

Clinical • Treatment costs • Human Immunodeficiency Virus • Infectious Disease • CD4

Recent report on indoles as a privileged anti-viral scaffold in drug discovery. (PubMed, Eur J Med Chem) - "Indole-containing drugs, such as enfuvirtide (T-20), arbidol, and delavirdine, have demonstrated significant efficacy in treating viral diseases. The review includes discussions on synthetic protocols, inhibitory concentrations, SAR study, and computational study. This review shall identify new antiviral indoles that may help to combat new viral threats in the future."

Journal • Review • Dengue Fever • Ebola Virus Disease • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Design of coiled-coil N-peptides against HIV-1 based on a CADD strategy. (PubMed, Org Biomol Chem) - "Nevertheless, the current market leader, Enfuvirtide, is facing numerous challenges in clinical application...Mechanistic investigations unveiled IZNP02QE's ability to disrupt the crucial endogenous 6-helix bundle (6-HB) by forming heteropolymers, underscoring its potential as a novel anti-HIV-1 agent. This work not only pioneers a novel design methodology for N-peptides but also opens up the possibility of a CADD strategy for designing peptide-based fusion inhibitors."

Journal • Human Immunodeficiency Virus • Infectious Disease

Citrullination modulation stabilizes HIF-1α to promote tumour progression. (PubMed, Nat Commun) - "Here, we find that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization. Furthermore, we identify that dihydroergotamine mesylate (DHE) acts as an antagonist of PADI4, which ultimately suppresses tumour progression. Collectively, our results reveal citrullination as a posttranslational modification related to HIF-1α stability, and suggest that targeting PADI4-mediated HIF-1α citrullination is a promising therapeutic strategy for cancers with aberrant HIF-1α expression."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Von Hippel-Lindau Syndrome • HIF1A • PADI4

The Challenge of Adherence to a Complex Antiretroviral Therapy Regimen in an Individual With Multidrug-Resistant HIV. (PubMed, Top Antivir Med) - "Despite various attempts to obtain sustained viral suppression, including the off-label administration of intravenous foscarnet and enfuvirtide, and thorough follow-up with 16 viral genotyping/phenotyping from 1999 to 2021, viral control was not maintained. Recently, the introduction of a regimen with fostemsavir and lenacapavir resulted in long-term viral suppression."

Adherence • Journal • Human Immunodeficiency Virus • Infectious Disease

Characteristics and outcomes of Virally Suppressed (VS) Treatment Experienced (VSTE) people with HIV (PWH) (AIDS 2024) - "Of PWH with results within 3 years, 78% had =1 major mutation (48% NRTIs, 44% NNRTIs, 26% PIs, 11% INSTIs); 44% =2 class resistance; most common mutations: M184VI (34%); A62V (33%); K103NS (22%).During follow-up (median 2.8 years), 5% had =1 VB and 6% had VF (more common on regimens >2 core classes, 9% vs 5% p2 Core ARV Classes1,082 (19%)243 (22%)74 (30%)93 (9%)VSTE: virologically suppressed treatment experienced; ARV: antiretroviral; HTE: heavily treatment experienced; STR: single tablet regimen; Core regimen classes: non-nucleoside reverse transcriptase inhibitors [NNRTIs], integrase inhibitors [INSTIs], nucleoside/nucleotide reverse transcriptase inhibitors [NRTIs], protease inhibitors [PIs].†Complex regimen: 2 out of 3 core classes (NNRTI, PI, INSTI), darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) or tenofovir disoproxil fumarate (TDF), multi-dosing per day, complex multi-pill regimen (excluding regimens reflecting available single-tablet..."

Human Immunodeficiency Virus • Infectious Disease