title: Different resistance mutations can be detected simultaneously in the blood and the lung of HIV-1 infected individuals on antiretroviral therapy.
abstract: In this retrospective study, matched peripheral blood and lung samples from patients on antiretroviral therapy were studied in order to investigate whether differences in mutations associated with resistance to nucleoside analogues could be detected between the lung and blood. Discordant mutation patterns in the reverse transcriptase (RT) between plasma and cell free bronchoalveolar lavage fluid (BAL-fluid) HIV-1 genomic RNA was observed in five out of seven patients on nucleoside reverse transcriptase inhibitor (NRTI) monotherapy and six out of seven on combination therapy. In the cellular compartments, DNA recovered from peripheral blood mononuclear cells (PBMCs) and cells from BAL-cells discordant HIV-1 resistance genotypes were detected in 15 out of 44 matched samples. Differences in resistant genotypes between PBMCs and BAL-cells were most pronounced in patients receiving combination antiretroviral therapy. The pattern and number of mutations in RT associated with resistance differed in the BAL-cells compared to PBMCs in four out of 12 subjects not receiving antiretroviral therapy at the time of bronchoscopy, three from 14 patients on NRTI monotherapy, five out of nine on dual combination therapy and three out of nine on HAART. The differences in the detection of resistance mutations between blood and the lung suggest that the lung is a site of replication for HIV-1.
authors.affiliation: Jefferiss Trust Laboratories, Wright-Fleming Institute, Faculty of Medicine, Imperial College School of Medicine, St. Mary's Hospital, London, United Kingdom.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: White
authors.forename: Dominique
authors.initials: D
authors.lastname: Israel-Biet
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Coker
authors.forename: David M
authors.initials: DM
authors.lastname: Mitchell
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Weber
authors.forename: John R
authors.initials: JR
authors.lastname: Clarke
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008168:Lung / Q000821:virology*; D009154:Mutation; D012367:RNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase