ArticleNature medicine2008
Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs.
Article in Nature medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
201 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Characterizing Class-Specific Exposure-Viral Load Suppression Response of HIV Antiretrovirals Using A Model-Based Meta-Analysis.Clinical and translational science · 2016Pooled it
- Safety, Tolerability, and Pharmacokinetics of Intravenous Doses of PF-07304814, a Phosphate Prodrug Protease Inhibitor for the Treatment of SARS-CoV-2, in Healthy Adult Participants.Clinical pharmacology in drug development · 2022Trial
- Impact of Pre-exposure History and Host Genetics on Antibody Avidity Following Norovirus Vaccination.The Journal of infectious diseases · 2017Trial
- Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial.The Journal of infectious diseases · 2013Trial
- From in vitro EC₅₀ to in vivo dose-response for antiretrovirals using an HIV disease model. Part I: a framework.Journal of pharmacokinetics and pharmacodynamics · 2012Trial
- Comparative evaluation of screening approaches for antiviral monoclonal antibody combinations.Journal of virology · 2026Article
- Scientific synergy between prophylactic and therapeutic HIV vaccines-prevention and cure.NPJ vaccines · 2026Article
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Autologous neutralizing antibodies and polyfunctional T cells contribute to long-term HIV-1 post-intervention control.Nature immunology · 2026Article
- Screening of the Pandemic Response Box Library Identified CRM1/XPO1 as an Anti-Mammarenavirus Druggable Target.Viruses · 2026Article
- A Darwinian model for the evolution of drug resistance to long-acting PrEP during an early HIV infection.PloS one · 2026Article
- Structure-Guided Design of Peptide Inhibitors Targeting Class I Viral Fusion Proteins.Pathogens (Basel, Switzerland) · 2025Review
- Broadly neutralizing human monoclonal antibodies against BK polyomavirus genotypes.The Journal of general virology · 2025Article
- Factors associated with resistance of HIV-1 reservoir viruses to neutralization by autologous IgG antibodies.The Journal of clinical investigation · 2025Article
- Article
- 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
- Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.Viruses · 2025Article
- Effects of the G-quadruplex-binding drugs quarfloxin and CX-5461 on the malaria parasite Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2023Article
- Application of the SLAPNAP statistical learning tool to broadly neutralizing antibody HIV prevention research.iScience · 2023Article
- HIV-1 protease inhibitors with a P1 phosphonate modification maintain potency against drug-resistant variants by increased interactions with flap residues.European journal of medicinal chemistry · 2023Article
141 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Highly active antiretroviral therapy (HAART) can control HIV-1 replication, but suboptimal treatment allows for the evolution of resistance and rebound viremia. A comparative measure of antiviral activity under clinically relevant conditions would guide drug development and the selection of regimens that maximally suppress replication. Here we show that current measures of antiviral activity, including IC(50) and inhibitory quotient, neglect a key dimension, the dose-response curve slope. Using infectivity assays with wide dynamic range, we show that this slope has noteworthy effects on antiviral activity. Slope values are class specific for antiviral drugs and define intrinsic limitations on antiviral activity for some classes. Nucleoside reverse transcriptase inhibitors and integrase inhibitors have slopes of approximately 1, characteristic of noncooperative reactions, whereas non-nucleoside reverse transcriptase inhibitors, protease inhibitors and fusion inhibitors unexpectedly show slopes >1. Instantaneous inhibitory potential (IIP), the log reduction in single-round infectivity at clinical drug concentrations, is strongly influenced by slope and varies by >8 logs for anti-HIV drugs. IIP provides a more accurate measure of antiviral activity and in general correlates with clinical outcomes. Only agents with slopes >1 achieve high-level inhibition of single-round infectivity, a finding with profound implications for drug and vaccine development.
Indexed as
Identifiers
What OpenQuestion holds
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.