title: Despite high concordance, distinct mutational and phenotypic drug resistance profiles in human immunodeficiency virus type 1 RNA are observed in gastrointestinal mucosal biopsy specimens and peripheral blood mononuclear cells compared with plasma.
abstract: The gastrointestinal mucosa is a major lymphoid tissue reservoir for human immunodeficiency virus (HIV) replication. Genotypic and phenotypic resistance patterns of HIV type 1 (HIV-1) RNA isolated from colonic mucosa were compared with those from the plasma and peripheral blood mononuclear cells (PBMC) of 7 patients. Genotyping was performed using full-sequence analysis, and phenotyping was performed using a recombinant virus assay. Mutations in the reverse-transcriptase (kappa=.84) and protease (kappa=.73) genes were highly concordant among compartments. Similarly, phenotypic resistance patterns were highly concordant among compartments (intraclass correlation coefficient,.91). In 5 instances among 3 patients, a different genotypic result was observed between plasma and the other tissue compartments. Mixtures of wild-type and mutated HIV-1 RNA were present in the mucosa and PBMC but not in the plasma. Despite significant concordance among compartments, mucosal- and PBMC-derived viral RNA showed instances of discordance with plasma-derived virus that may suggest compartmentalization of virus.
authors.affiliation: School of Medicine, Department of Medicine, University of California Los Angeles (UCLA) Center for HIV and Digestive Diseases and UCLA AIDS Institute, Los Angeles, CA 90095, USA. mpoles@ucla.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Poles
authors.forename: J
authors.initials: J
authors.lastname: Elliott
authors.forename: J
authors.initials: J
authors.lastname: Vingerhoets
authors.forename: L
authors.initials: L
authors.lastname: Michiels
authors.forename: A
authors.initials: A
authors.lastname: Scholliers
authors.forename: S
authors.initials: S
authors.lastname: Bloor
authors.forename: B
authors.initials: B
authors.lastname: Larder
authors.forename: K
authors.initials: K
authors.lastname: Hertogs
authors.forename: P A
authors.initials: PA
authors.lastname: Anton
mesh_terms: D000328:Adult; D002908:Chronic Disease; D003106:Colon / Q000821:virology; D004351:Drug Resistance / Q000235:genetics; D005753:Gastric Mucosa / Q000821:virology*; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011480:Protease Inhibitors / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
chemical_list: D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors