ArticleAIDS research and human retroviruses2015
Anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates.
Article in AIDS research and human retroviruses, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05850728 (First in Human Clinical Trial of a Next Generation, Long-acting Injectable, Combination Antiretroviral Therapy Platform), which is not on this map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
First in Human Clinical Trial of a Next Generation, Long-acting Injectable, Combination Antiretroviral Therapy Platform
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Analysis of multi-drug cancer nanomedicine.Nature nanotechnology · 2025Pooled it
- A novel all-in-one injectable composed of tenofovir alafenamide-dolutegravir-lamivudine exhibits long-acting plasma and cell drug persistence for 8 weeks.AIDS (London, England) · 2026Article
- Harnessing albumin as a carrier for the delivery of anti-HIV drugs to the lymphatic system.Acta biomaterialia · 2026Article
- Polymeric and lipidic nanoparticles in transforming anti-HIV combinational therapy: can they turn the tide?Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Recent Advances in Antiviral Drug Delivery Strategies.AAPS PharmSciTech · 2025Review
- Tailoring biomaterials for vaccine delivery.Journal of nanobiotechnology · 2024Review
- Physiologically based Pharmacokinetic Model Validated to Enable Predictions Of Multiple Drugs in a Long-acting Drug-combination Nano-Particles (DcNP): Confirmation with 3 HIV Drugs, Lopinavir, Ritonavir, and Tenofovir in DcNP Products.Journal of pharmaceutical sciences · 2024Article
- Chronic Hepatitis B Infection: New Approaches towards Cure.Biomolecules · 2023Review
- Long-Acting Treatments for Hepatitis B.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Challenges and opportunities in metastatic breast cancer treatments: Nano-drug combinations delivered preferentially to metastatic cells may enhance therapeutic response.Pharmacology & therapeutics · 2022Review
- Physiologically Based Pharmacokinetic Modeling of 3 HIV Drugs in Combination and the Role of Lymphatic System after Subcutaneous Dosing. Part 2: Model for the Drug-combination Nanoparticles.Journal of pharmaceutical sciences · 2022Article
- Prodrug Therapies for Infectious and Neurodegenerative Diseases.Pharmaceutics · 2022Review
- Physiologically Based Pharmacokinetic Modeling of 3 HIV Drugs in Combination and the Role of Lymphatic System after Subcutaneous Dosing. Part 1: Model for the Free-Drug Mixture.Journal of pharmaceutical sciences · 2022Article
- The quest for a better fight: How can nanomaterials address the current therapeutic and diagnostic obstacles in the fight against COVID-19?Journal of drug delivery science and technology · 2022Review
- Nanotechnology advances in pathogen- and host-targeted antiviral delivery: multipronged therapeutic intervention for pandemic control.Drug delivery and translational research · 2021Review
- Pharmacology of HIV Cure: Site of Action.Clinical pharmacology and therapeutics · 2021Review
- Nanotechnology approaches for global infectious diseases.Nature nanotechnology · 2021Review
- The Lymph Node Reservoir: Physiology, HIV Infection, and Antiretroviral Therapy.Clinical pharmacology and therapeutics · 2021Review
- A Concept Evaluation Study of a New Combination Bictegravir plus Tenofovir Alafenamide Nanoformulation with Prolonged Sustained-Drug-Release Potency for HIV-1 Preexposure Prophylaxis.Antimicrobial agents and chemotherapy · 2021Article
- Gene Transfer in Adeno-Associated Virus Seropositive Rhesus Macaques Following Rapamycin Treatment and Subcutaneous Delivery of AAV6, but Not Retargeted AAV6 Vectors.Human gene therapy · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
HIV patients on combination oral drug therapy experience insufficient drug levels in lymph nodes, which is linked to viral persistence. Following success in enhancing lymph node drug levels and extending plasma residence time of indinavir formulated in lipid nanoparticles, we developed multidrug anti-HIV lipid nanoparticles (anti-HIV LNPs) containing lopinavir (LPV), ritonavir (RTV), and tenofovir (PMPA). These anti-HIV LNPs were prepared, characterized, scaled up, and evaluated in primates with a focus on plasma time course and intracellular drug exposure in blood and lymph nodes. Four macaques were subcutaneously administered anti-HIV LNPs and free drug suspension in a crossover study. The time course of the plasma drug concentration as well as intracellular drug concentrations in blood and inguinal lymph nodes were analyzed to compare the effects of LNP formulation. Anti-HIV LNPs incorporated LPV and RTV with high efficiency and entrapped a reproducible fraction of hydrophilic PMPA. In primates, anti-HIV LNPs produced over 50-fold higher intracellular concentrations of LPV and RTV in lymph nodes compared to free drug. Plasma and intracellular drug levels in blood were enhanced and sustained up to 7 days, beyond that achievable by their free drug counterpart. Thus, multiple antiretroviral agents can be simultaneously incorporated into anti-HIV lipid nanoparticles to enhance intracellular drug concentrations in blood and lymph nodes, where viral replication persists. As these anti-HIV lipid nanoparticles also prolonged plasma drug exposure, they hold promise as a long-acting dosage form for HIV patients in addressing residual virus in cells and tissue.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.