4.7 Article Proceedings Paper

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

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 183, Issue 1, Pages 143-148

Publisher

UNIV CHICAGO PRESS
DOI: 10.1086/317640

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Funding

  1. NIAID NIH HHS [AI-28697, AI-01668, AI-01610] Funding Source: Medline
  2. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K24AI001610, P30AI028697] Funding Source: NIH RePORTER

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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.

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