ArticleAntimicrobial agents and chemotherapy2004
Natural variation of drug susceptibility in wild-type human immunodeficiency virus type 1.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.Clinical pharmacokinetics · 2014Pooled it
- Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Nairobi, Kenya.The Journal of infectious diseases · 2019Trial
- Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations.Journal of clinical pharmacology · 2014Trial
- Therapeutic levels of lopinavir in late pregnancy and abacavir passage into breast milk in the Mma Bana Study, Botswana.Antiviral therapy · 2013Trial
- Pharmacokinetic modelling of efavirenz, atazanavir, lamivudine and tenofovir in the female genital tract of HIV-infected pre-menopausal women.Clinical pharmacokinetics · 2012Trial
- Article
- HIV-1 Sub-subtype A6 Remains Susceptible to Second-Generation Integrase Inhibitors With Limited Emergence of Resistance in Vitro.Open forum infectious diseases · 2026Article
- Potential role of doravirine for the treatment of HIV-1-infected persons with transmitted drug resistance.AIDS research and therapy · 2023Article
- Human Immunodeficiency Virus Drug Resistance: 2018 Recommendations of the International Antiviral Society-USA Panel.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- The Utility of Efavirenz-based Prophylaxis Against HIV Infection. A Systems Pharmacological Analysis.Frontiers in pharmacology · 2019Article
- A Mathematical Model to Predict HIV Virological Failure and Elucidate the Role of Lymph Node Drug Penetration.CPT: pharmacometrics & systems pharmacology · 2017Article
- Determination of Phenotypic Resistance Cutoffs From Routine Clinical Data.Journal of acquired immune deficiency syndromes (1999) · 2017Article
- Collaborative update of a rule-based expert system for HIV-1 genotypic resistance test interpretation.PloS one · 2017Article
- Breast milk pharmacokinetics of efavirenz and breastfed infants' exposure in genetically defined subgroups of mother-infant pairs: an observational study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2015Observational
- Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2015Article
- Maternal and fetal zidovudine pharmacokinetics during pregnancy and labour: too high dose infused at labour?British journal of clinical pharmacology · 2014Article
- Role of the K101E substitution in HIV-1 reverse transcriptase in resistance to rilpivirine and other nonnucleoside reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2013Article
- Protein-free efavirenz concentrations in cerebrospinal fluid and blood plasma are equivalent: applying the law of mass action to predict protein-free drug concentration.Antimicrobial agents and chemotherapy · 2013Article
- Compartmentalization and antiviral effect of efavirenz metabolites in blood plasma, seminal plasma, and cerebrospinal fluid.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Sequence and structure based models of HIV-1 protease and reverse transcriptase drug resistance.BMC genomics · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or "biological cutoffs," for the PhenoSense HIV phenotypic drug susceptibility assay. Definition of the natural variation in drug susceptibility in wild-type human immunodeficiency virus (HIV) type 1 isolates is necessary to determine the prevalence of innate drug resistance and to assess the capability of the PhenoSense assay to reliably measure subtle reductions in drug susceptibility. The biological cutoffs for each drug, defined by the 99th percentile of the fold change in the 50% inhibitory concentration distributions or the mean fold change plus 2 standard deviations, were lower than those previously reported for other phenotypic assays and lower than the clinically relevant cutoffs previously defined for the PhenoSense assay. The 99th percentile fold change values ranged from 1.2 (tenofovir) to 1.8 (zidovudine) for nucleoside reverse transcriptase RT inhibitors (RTIs), from 3.0 (efavirenz) to 6.2 (delavirdine) for nonnucleoside RTIs, and from 1.6 (lopinavir) to 3.6 (nelfinavir) for protease inhibitors. To evaluate the potential role of intrinsic assay variability in the observed variations in the drug susceptibilities of wild-type isolates, 10 reference viruses with different drug susceptibility patterns were tested 8 to 30 times each. The median coefficients of variation in fold change for the reference viruses ranged from 12 to 18% for all drugs except zidovudine (32%), strongly suggesting that the observed differences in wild-type virus susceptibility to the different drugs is related to intrinsic virus variability rather than assay variability. The low biological cutoffs and assay variability suggest that the PhenoSense HIV assay may assist in defining clinically relevant susceptibility cutoffs for resistance to antiretroviral drugs.
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