ArticleNature medicine2012
A quantitative basis for antiretroviral therapy for HIV-1 infection.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 2 of them syntheses that pooled it.
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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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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
106 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Current trends and future directions in probiotics research for HIV/AIDS.Frontiers in microbiology · 2024Pooled it
- A Meta-analysis of Passive Immunization Studies Shows that Serum-Neutralizing Antibody Titer Associates with Protection against SHIV Challenge.Cell host & microbe · 2019Pooled it
- Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial.Nature medicine · 2021Trial
- 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
- Comparative evaluation of screening approaches for antiviral monoclonal antibody combinations.Journal of virology · 2026Article
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Prediction of HIV-1 sensitivity to broadly neutralizing antibodies using statistical distribution sampling (SDS) technology.BMC bioinformatics · 2026Article
- Autologous neutralizing antibodies and polyfunctional T cells contribute to long-term HIV-1 post-intervention control.Nature immunology · 2026Article
- Model-informed prediction of antiviral drug combination synergy from sparse data using complementary mechanistic and pharmacodynamic approaches.Frontiers in pharmacology · 2026Article
- A Darwinian model for the evolution of drug resistance to long-acting PrEP during an early HIV infection.PloS one · 2026Article
- Factors associated with resistance of HIV-1 reservoir viruses to neutralization by autologous IgG antibodies.The Journal of clinical investigation · 2025Article
- A comprehensive engineering strategy improves potency and manufacturability of a near pan-neutralizing antibody against HIV.Structure (London, England : 1993) · 2025Article
- Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.Viruses · 2025Article
- A multi-informant qualitative analysis of desired features for an mHealth tool for youth living with HIV in South Carolina.Journal of pediatric psychology · 2024Article
- Two-way pharmacodynamic modeling of drug combinations and its application to pairs of repurposed Ebola and SARS-CoV-2 agents.Antimicrobial agents and chemotherapy · 2024Article
- Article
- Machine learning aided multiscale modelling of the HIV-1 infection in the presence of NRTI therapy.PeerJ · 2023Article
- Article
- Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2.Microbiology spectrum · 2022Article
- Genome-wide CRISPR screens identify combinations of candidate latency reversing agents for targeting the latent HIV-1 reservoir.Science translational medicine · 2022Article
46 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
Highly active antiretroviral therapy (HAART) has dramatically decreased mortality from HIV-1 infection and is a major achievement of modern medicine. However, there is no fundamental theory of HAART. Elegant models describe the dynamics of viral replication, but a metric for the antiviral activity of drug combinations relative to a target value needed for control of replication is lacking. Treatment guidelines are based on empirical results of clinical trials in which other factors such as regimen tolerability also affect outcome. Why only certain drug combinations control viral replication remains unclear. Here we quantify the intrinsic antiviral activity of antiretroviral drug combinations. We show that most single antiretroviral drugs show previously unappreciated complex nonlinear pharmacodynamics that determine their inhibitory potential at clinical concentrations. We demonstrate that neither of the major theories for drug combinations accurately predicts the combined effects of multiple antiretrovirals. However, the combined effects can be understood with a new approach that considers the degree of independence of drug effects. This analysis allows a direct comparison of the inhibitory potential of different drug combinations under clinical concentrations, reconciles the results of clinical trials, defines a target level of inhibition associated with treatment success and provides a rational basis for treatment simplification and optimization.
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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.