ArticlePLoS computational biology2019
Mechanistic framework predicts drug-class specific utility of antiretrovirals for HIV prophylaxis.
Article in PLoS computational biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Pharmacological markers of HIV prevention for oral pre-exposure prophylaxis in men who have sex with men.Nature communications · 2026Article
- Pharmacokinetics, Pharmacodynamics, Efficacy and Drug Resistance Selection of Injectable Long-Acting Lenacapavir Pre-Exposure Prophylaxis (PrEP) Against HIV.CPT: pharmacometrics & systems pharmacology · 2026Article
- Pharmacokinetics, pharmacodynamics, efficacy and drug resistance selection of injectable long-acting lenacapavir pre-exposure prophylaxis (PrEP) against HIV.medRxiv : the preprint server for health sciences · 2025Article
- Modelling the impact of initiation delay, duration and prior PrEP on the efficacy of post-exposure prophylaxis containing a tenofovir/emtricitabine backbone.Journal of the International AIDS Society · 2025Article
- Modeling of HIV-1 prophylactic efficacy and toxicity with islatravir shows non-superiority for oral dosing, but promise as a subcutaneous implant.CPT: pharmacometrics & systems pharmacology · 2024Article
- Model-based predictions of protective HIV pre-exposure prophylaxis adherence levels in cisgender women.Nature medicine · 2023Article
- Numerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemes.PLoS computational biology · 2021Article
- Success of prophylactic antiviral therapy for SARS-CoV-2: Predicted critical efficacies and impact of different drug-specific mechanisms of action.PLoS computational biology · 2021Article
- Validation and clinical application of a method to quantify efavirenz in cervicovaginal secretions from flocked swabs using liquid chromatography tandem mass spectrometry.Wellcome open research · 2021Article
- Mathematical modeling to reveal breakthrough mechanisms in the HIV Antibody Mediated Prevention (AMP) trials.PLoS computational biology · 2020Article
- Modeling HIV Pre-Exposure Prophylaxis.Frontiers in pharmacology · 2019Review
- The Utility of Efavirenz-based Prophylaxis Against HIV Infection. A Systems Pharmacological Analysis.Frontiers in pharmacology · 2019Article
- Hybrid stochastic framework predicts efficacy of prophylaxis against HIV: An example with different dolutegravir prophylaxis schemes.PLoS computational biology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, there is no effective vaccine to halt HIV transmission. However, pre-exposure prophylaxis (PrEP) with the drug combination Truvada can substantially decrease HIV transmission in individuals at risk. Despite its benefits, Truvada-based PrEP is expensive and needs to be taken once-daily, which often leads to inadequate adherence and incomplete protection. These deficits may be overcome by next-generation PrEP regimen, including currently investigated long-acting formulations, or patent-expired drugs. However, poor translatability of animal- and ex vivo/in vitro experiments, and the necessity to conduct long-term (several years) human trials involving considerable sample sizes (N>1000 individuals) are major obstacles to rationalize drug-candidate selection. We developed a prophylaxis modelling tool that mechanistically considers the mode-of-action of all available drugs. We used the tool to screen antivirals for their prophylactic utility and identify lower bound effective concentrations that can guide dose selection in PrEP trials. While in vitro measurable drug potency usually guides PrEP trial design, we found that it may over-predict PrEP potency for all drug classes except reverse transcriptase inhibitors. While most drugs displayed graded concentration-prophylaxis profiles, protease inhibitors tended to switch between none- and complete protection. While several treatment-approved drugs could be ruled out as PrEP candidates based on lack-of-prophylactic efficacy, darunavir, efavirenz, nevirapine, etravirine and rilpivirine could more potently prevent infection than existing PrEP regimen (Truvada). Notably, some drugs from this candidate set are patent-expired and currently neglected for PrEP repurposing. A next step is to further trim this candidate set by ruling out compounds with ominous safety profiles, to assess different administration schemes in silico and to test the remaining candidates in human trials.
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