ArticleAntimicrobial agents and chemotherapy2012
Novel method to assess antiretroviral target trough concentrations using in vitro susceptibility data.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Is infant exposure to antiretroviral drugs during breastfeeding quantitatively important? A systematic review and meta-analysis of pharmacokinetic studies.The Journal of antimicrobial chemotherapy · 2015Pooled it
- Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.Clinical pharmacokinetics · 2014Pooled it
- Pharmacokinetic and Safety Profile of the Novel HIV Nonnucleoside Reverse Transcriptase Inhibitor MK-8507 in Adults without HIV.Antimicrobial agents and chemotherapy · 2021Trial
- Fosamprenavir with Ritonavir Pharmacokinetics during Pregnancy.Antimicrobial agents and chemotherapy · 2020Trial
- Trial
- Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.Journal of clinical pharmacology · 2014Trial
- Clinical and genetic determinants of plasma nevirapine exposure following an intrapartum dose to prevent mother-to-child HIV transmission.The Journal of infectious diseases · 2013Trial
- Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents.AIDS (London, England) · 2011Trial
- Heterogeneous Antiretroviral Drug Exposure in Male and Female Genital Tract Tissues.The Journal of infectious diseases · 2025Article
- Antiretroviral drug exposure in lymph nodes is heterogeneous and drug dependent.Journal of the International AIDS Society · 2022Article
- Toward Consensus on Correct Interpretation of Protein Binding in Plasma and Other Biological Matrices for COVID-19 Therapeutic Development.Clinical pharmacology and therapeutics · 2021Review
- Quantitative Imaging Analysis of the Spatial Relationship between Antiretrovirals, Reverse Transcriptase Simian-Human Immunodeficiency Virus RNA, and Collagen in the Mesenteric Lymph Nodes of Nonhuman Primates.Antimicrobial agents and chemotherapy · 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
- Antiretroviral concentrations and surrogate measures of efficacy in the brain tissue and CSF of preclinical species.Xenobiotica; the fate of foreign compounds in biological systems · 2019Article
- A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women.Clinical pharmacokinetics · 2018Article
- In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents.Clinical pharmacokinetics · 2018Article
- Article
- A Mathematical Model to Predict HIV Virological Failure and Elucidate the Role of Lymph Node Drug Penetration.CPT: pharmacometrics & systems pharmacology · 2017Article
- Pharmacokinetics of Once-Daily Darunavir/Ritonavir With and Without Etravirine in Human Immunodeficiency Virus-Infected Children, Adolescents, and Young Adults.Journal of the Pediatric Infectious Diseases Society · 2016Article
- Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Durable suppression of HIV-1 replication requires the establishment of antiretroviral drug concentrations that exceed the susceptibility of the virus strain(s) infecting the patient. Minimum plasma drug concentrations (C(trough)) are correlated with response, but determination of target C(trough) values is hindered by a paucity of in vivo concentration-response data. In the absence of these data, in vitro susceptibility measurements, adjusted for serum protein binding, can provide estimations of suppressive in vivo drug concentrations. We derived serum protein binding correction factors (PBCF) for protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and an integrase inhibitor by measuring the effect of a range of human serum concentrations on in vitro drug susceptibility measured with the PhenoSense HIV assay. PBCFs corresponding to 100% HS were extrapolated using linear regression and ranged from 1.4 for nevirapine to 77 for nelfinavir. Using the mean 95% inhibitory concentration (IC(95)) for ≥1,200 drug-susceptible viruses, we calculated protein-bound IC(95) (PBIC(95)) values. PBIC(95) values were concordant with the minimum effective C(trough) values that were established in well-designed pharmacodynamic studies (e.g., indinavir, saquinavir, and amprenavir). In other cases, the PBIC(95) values were notably lower (e.g., darunavir, efavirenz, and nevirapine) or higher (nelfinavir and etravirine) than existing target recommendations. The establishment of PBIC(95) values as described here provides a convenient and standardized approach for estimation of the minimum drug exposure that is required to maintain viral suppression and prevent the emergence of drug-resistant variants, particularly when in vivo concentration-response relationships are lacking.
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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.