ArticleJournal of virology2011
One percent tenofovir applied topically to humanized BLT mice and used according to the CAPRISA 004 experimental design demonstrates partial protection from vaginal HIV infection, validating the BLT model for evaluation of new microbicide candidates.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 136 citations in OpenAlex.
- Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness.Journal of acquired immune deficiency syndromes (1999) · 2015Trial
- Preclinical Pharmacokinetics of a Triple-Combination Intravaginal Ring for HIV Prevention.Pharmaceutics · 2026Article
- The Gut Microbiome in HIV Pathogenesis: Interconnections Between Dysbiosis, Immune Dysfunction, and Viral Persistence.International journal of molecular sciences · 2026Review
- The promise and perils of humanized mice: workshop report from the 29th scientific conference of the society on NeuroImmune pharmacology (SNIP).NeuroImmune pharmacology and therapeutics · 2025Article
- A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection.Nature biotechnology · 2024Article
- Progress in building clinically relevant patient-derived tumor xenograft models for cancer research.Animal models and experimental medicine · 2023Review
- The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?Pathogens (Basel, Switzerland) · 2023Review
- Loss of In Vivo Replication Fitness of HIV-1 Variants Resistant to the Tat Inhibitor, dCA.Viruses · 2023Article
- Acute antagonism in three-drug combinations for vaginal HIV prevention in humanized mice.Scientific reports · 2023Article
- Translational Models to Predict Target Concentrations for Pre-Exposure Prophylaxis in Women.AIDS research and human retroviruses · 2022Review
- Comparing Current and Next-Generation Humanized Mouse Models for Advancing HIV and HIV/Viruses · 2022Article
- Baseline and time-updated factors in preclinical development of anionic dendrimers as successful anti-HIV-1 vaginal microbicides.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2022Review
- Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension.Frontiers in immunology · 2022Article
- Impact of human immunodeficiency virus on pulmonary vascular disease.Global cardiology science & practice · 2021Review
- Humanized Mice for the Evaluation of Novel HIV-1 Therapies.Frontiers in immunology · 2021Review
- The Microbiome as a Key Regulator of Female Genital Tract Barrier Function.Frontiers in cellular and infection microbiology · 2021Review
- Modeling oncogenic herpesvirus infections in humanized mice.Current opinion in virology · 2020Review
- Highly synergistic drug combination prevents vaginal HIV infection in humanized mice.Scientific reports · 2020Article
- 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
- Impact of Suboptimal APOBEC3G Neutralization on the Emergence of HIV Drug Resistance in Humanized Mice.Journal of virology · 2020Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 7 institutions in 1 country.
Funding
Abstract
Recent iPrEx clinical trial results provided evidence that systemic preexposure prophylaxis (PrEP) with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) can partially prevent rectal HIV transmission in humans. Similarly, we have previously demonstrated that systemic administration of the same FTC-TDF combination efficiently prevented rectal transmission in humanized bone marrow/liver/thymus (BLT) mice. The CAPRISA 004 trial recently demonstrated that topical application of the tenofovir could partially prevent vaginal HIV-1 transmission in humans. To further validate the usefulness of the BLT mouse model for testing HIV prevention strategies, we evaluated the topical administration of tenofovir as used in CAPRISA 004 to prevent vaginal HIV transmission in BLT mice. Our results demonstrate that vaginally administered 1% tenofovir significantly reduced HIV transmission in BLT mice (P = 0.002). Together with the results obtained after systemic antiretroviral PrEP, these topical inhibitor data serve to validate the use of humanized BLT mice to evaluate both systemic and topical inhibitors of HIV transmission. Based on these observations, we tested six additional microbicide candidates for their ability to prevent vaginal HIV transmission: a C-peptide fusion inhibitor (C52L), a membrane-disrupting amphipathic peptide inhibitor (C5A), a trimeric d-peptide fusion inhibitor (PIE12-Trimer), a combination of reverse transcriptase inhibitors (FTC-TDF), a thioester zinc finger inhibitor (TC247), and a small-molecule Rac inhibitor (NSC23766). No protection was seen with the Rac inhibitor NSC23766. The thioester compound TC247 offered partial protection. Significant protection was afforded by FTC-TDF, and complete protection was offered by three different peptide inhibitors tested. Our results demonstrate that these effective topical inhibitors have excellent potential to prevent vaginal HIV transmission in humans.
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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.