ABSTRACT
OBJECTIVE: Emergence of human immunodeficiency virus type-1 (HIV-1) genotypic drug resistance is generally attributed to noncompliance, poorly absorbed drugs, or drug-to-drug interaction. Attempts to determine emerging genotypic drug resistance from study subjects on highly active antiretroviral therapy (HAART) relied on insensitive polymerase chain reaction (PCR) techniques, revealing wild type HIV-1 or precursor resistant genotypes from few plasma samples successfully amplified with <50 copies/mL. STUDY DESIGN/METHODS: In this analysis, using Applied Biosystems' ViroSeq HIV-1 Genotyping Systems, Version 2.0 (Applied Biosystems, Foster City, CA, USA) and the supplemental, for research use only, nested PCR primers, genotypic drug resistance was determined in longitudinal plasma samples from 11 study subjects on HAART. RESULTS: In 4 of 11 study subjects, newly emerging genotypic primary resistant mutations were detected in plasma samples with <50 copies/mL. Most of these primary drug-resistant mutations were detected in subsequent longitudinal samples with detectable viral load (viral breakthrough). CONCLUSIONS: This analysis suggests sufficient viral replication <50 copies/mL to generate genotypic drug resistance in study subjects on suppressive HAART.
Subject(s)
Anti-HIV Agents/pharmacology , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV-1/drug effects , Mutation , RNA, Viral/drug effects , Reverse Transcriptase Inhibitors/pharmacology , Antiretroviral Therapy, Highly Active , Genotype , HIV Infections/drug therapy , HIV Protease Inhibitors/pharmacology , HIV-1/classification , HIV-1/genetics , Humans , Indinavir/pharmacology , Lamivudine/pharmacology , Longitudinal Studies , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/pharmacology , Viral Load , Zidovudine/pharmacologySubject(s)
DNA, Viral/genetics , Genetic Heterogeneity , HIV Envelope Protein gp120/genetics , HIV-1/genetics , Peptide Fragments/genetics , Amino Acid Sequence , Argentina , HIV Envelope Protein gp120/chemistry , HIV-1/chemistry , HIV-1/classification , Humans , Molecular Sequence Data , Peptide Fragments/chemistry , Phylogeny , Sequence Homology, Amino AcidABSTRACT
We monitored plasma levels of gentamycin in 28 patients being treated for different infectious processes. The mean age was 53.7 years. Drug dose and administration was determined by the treating physician, without knowledge of plasma levels. Peak and through levels were measured by RIA after the third and 7th dose. No patient had adequate therapeutic levels throughout the treatment period and 6 were therapeutic failures. Patients with renal insufficiency frequently had toxic plasma levels. Monitoring gentamycin plasma levels is recommended for all patients receiving the drug, especially those with renal insufficiency or therapeutic failure.
