ArticleThe Journal of antimicrobial chemotherapy2016
A long-acting formulation of the integrase inhibitor raltegravir protects humanized BLT mice from repeated high-dose vaginal HIV challenges.
Article in The Journal of antimicrobial chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- In Vitro Pharmacokinetic Properties of MK-2048, a Potent Drug Candidate for HIV Prevention.Viruses · 2026Article
- Article
- HIV-1 transmission: modelling and direct visualization in the third dimension.Microscopy (Oxford, England) · 2023Review
- Novel Perspectives on the Design and Development of a Long-Acting Subcutaneous Raltegravir Injection for Treatment of HIV-In Vitro and In Vivo Evaluation.Pharmaceutics · 2023Article
- Translational Models to Predict Target Concentrations for Pre-Exposure Prophylaxis in Women.AIDS research and human retroviruses · 2022Review
- Tolerability and Adherence of Antiretroviral Regimens Containing Long-Acting Fusion Inhibitor Albuvirtide for HIV Post-Exposure Prophylaxis: A Cohort Study in China.Infectious diseases and therapy · 2021Article
- Humanized Mice for Infectious and Neurodegenerative disorders.Retrovirology · 2021Review
- Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies.Retrovirology · 2020Review
- Translational Approach to Predicting the Efficacy of Maraviroc-Based Regimens as HIV Preexposure Prophylaxis.Antimicrobial agents and chemotherapy · 2020Article
- Advances in Humanized Mouse Models to Improve Understanding of HIV-1 Pathogenesis and Immune Responses.Frontiers in immunology · 2020Review
- Precision mouse models with expanded tropism for human pathogens.Nature biotechnology · 2019Article
- Long-Acting Anti-HIV Drugs Targeting HIV-1 Reverse Transcriptase and Integrase.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Pharmacology of Antiretrovirals in the Female Genital Tract for HIV Prevention.Journal of clinical pharmacology · 2018Review
- Ultra-long-acting removable drug delivery system for HIV treatment and prevention.Nature communications · 2018Article
- Raltegravir blocks the infectivity of red-fluorescent-protein (mCherry)-labeled HIV-1Antiviral research · 2018Article
- Long acting systemic HIV pre-exposure prophylaxis: an examination of the field.Drug delivery and translational research · 2017Review
- Humanized Mouse Models for Human Immunodeficiency Virus Infection.Annual review of virology · 2017Review
- Long-Acting Antiretrovirals: Where Are We now?Current HIV/AIDS reports · 2017Review
- Predicting HIV Pre-exposure Prophylaxis Efficacy for Women using a Preclinical Pharmacokinetic-Pharmacodynamic In Vivo Model.Scientific reports · 2017Article
- Humanized mice for HIV and AIDS research.Current opinion in virology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesPre-exposure prophylaxis (PrEP) using antiretroviral drugs (ARVs) has been shown to reduce HIV transmission in people at high risk of HIV infection. Adherence to PrEP strongly correlates with the level of HIV protection. Long-acting injectable ARVs provide sustained systemic drug exposures over many weeks and can improve adherence due to infrequent parenteral administration. Here, we evaluated a new long-acting formulation of raltegravir for prevention of vaginal HIV transmission.
methodsLong-acting raltegravir was administered subcutaneously to BALB/c, NSG (NOD-scid-gamma) and humanized BLT (bone marrow-liver-thymus) mice and rhesus macaques. Raltegravir concentration in peripheral blood and tissue was analysed. Suppression of HIV replication was assessed in infected BLT mice. Two high-dose HIV vaginal challenges were used to evaluate protection from HIV transmission in BLT mice.
resultsTwo weeks after a single subcutaneous injection of long-acting raltegravir in BLT mice (7.5 mg) and rhesus macaques (160 mg), the plasma concentration of raltegravir was comparable to 400 mg orally, twice daily in humans. Serum collected from mice 3 weeks post-administration of long-acting raltegravir efficiently blocked HIV infection of TZM-bl indicator cells in vitro. Administration of long-acting raltegravir suppressed viral RNA in plasma and cervico-vaginal fluids of infected BLT mice, demonstrating penetration of active raltegravir into the female reproductive tract. Using transmitted/founder HIV we observed that BLT mice administered a single subcutaneous dose of long-acting raltegravir were protected from two high-dose HIV vaginal challenges 1 week and 4 weeks after drug administration.
conclusionsThese preclinical results demonstrated the efficacy of long-acting raltegravir in preventing vaginal HIV transmission.
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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.