ArticleScientific reports2017
Predicting HIV Pre-exposure Prophylaxis Efficacy for Women using a Preclinical Pharmacokinetic-Pharmacodynamic In Vivo Model.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
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Who cites it
6 citing papers in PubMed.
- In situ analysis of neuronal injury and neuroinflammation during HIV-1 infection.Retrovirology · 2024Article
- A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection.Nature biotechnology · 2024Article
- A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention.CPT: pharmacometrics & systems pharmacology · 2023Article
- HIV co-infection augments EBV-induced tumorigenesisFrontiers in virology (Lausanne, Switzerland) · 2022Article
- Update on HIV Preexposure Prophylaxis: Effectiveness, Drug Resistance, and Risk Compensation.Current infectious disease reports · 2019Review
- Comparing Self-Report Pre-Exposure Prophylaxis Adherence Questions to Pharmacologic Measures of Recent and Cumulative Pre-Exposure Prophylaxis Exposure.Frontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The efficacy of HIV pre-exposure prophylaxis (PrEP) relies on adherence and may also depend on the route of HIV acquisition. Clinical studies of systemic tenofovir disoproxil fumarate (TDF) PrEP revealed reduced efficacy in women compared to men with similar degrees of adherence. To select the most effective PrEP strategies, preclinical studies are critically needed to establish correlations between drug concentrations (pharmacokinetics [PK]) and protective efficacy (pharmacodynamics [PD]). We utilized an in vivo preclinical model to perform a PK-PD analysis of systemic TDF PrEP for vaginal HIV acquisition. TDF PrEP prevented vaginal HIV acquisition in a dose-dependent manner. PK-PD modeling of tenofovir (TFV) in plasma, female reproductive tract tissue, cervicovaginal lavage fluid and its intracellular metabolite (TFV diphosphate) revealed that TDF PrEP efficacy was best described by plasma TFV levels. When administered at 50 mg/kg, TDF achieved plasma TFV concentrations (370 ng/ml) that closely mimicked those observed in humans and demonstrated the same risk reduction (70%) previously attained in women with high adherence. This PK-PD model mimics the human condition and can be applied to other PrEP approaches and routes of HIV acquisition, accelerating clinical implementation of the most efficacious PrEP strategies.
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Registered trials
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