title: Cytotoxic chemotherapy and the evolution of cellular and viral resistance to antiretroviral therapy in HIV- infected individuals with lymphoma.
abstract: The use of combination antiretroviral therapy (cART) and cytotoxic chemotherapy for HIV-associated lymphoma runs the risks of inducing HIV drug resistance. This study examined two possible mechanisms: altered expression of membrane drug transporter protein (MTP) and acquisition of mutations in pro-viral DNA.
  
  
  
  Expression levels of MTP and pro-viral DNA resistance mutation analysis were performed on peripheral blood mononuclear cells (PBMC) before, during, and after chemotherapy.
  
  
  
  Twenty nine patients completed the three time point estimations. There were no significant variations before, during, and after chemotherapy in the expression of four MTPs: ABCB1, ABCC1, ABCC2, and SLCO3A1 (OATP3A1). Pro-viral DNA sequencing revealed that only one patient developed a new nucleos/tide reverse transcriptase inhibitor-associated mutation (184V) during the course of the study, giving a mutation rate of 0.0027 per person per year.
  
  
  
  In conclusion, concomitant administration of cytotoxic chemotherapy and cART does not induce expression of MTP. Furthermore, no significant changes in viral resistance were observed pre- and post-chemotherapy, suggesting mutagenic cytotoxic chemotherapy seems not to induce mutations in HIV pro-viral DNA.
authors.affiliation: a Imperial College Faculty of Medicine , London , UK.|c Chelsea and Westmsinter/Imperial College Healthcare NHS Trust , London , UK.|e Centre for Immunology and Vaccinology, Imperial College London , London , UK.
authors.forename: Katie
authors.initials: K
authors.lastname: McFaul
authors.affiliation: b Department of Molecular & Clinical Pharmacology , University of Liverpool , Liverpool , UK.
authors.forename: Neill
authors.initials: N
authors.lastname: Liptrott
authors.affiliation: c Chelsea and Westmsinter/Imperial College Healthcare NHS Trust , London , UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Cox
authors.affiliation: b Department of Molecular & Clinical Pharmacology , University of Liverpool , Liverpool , UK.
authors.forename: Phillip
authors.initials: P
authors.lastname: Martin
authors.affiliation: b Department of Molecular & Clinical Pharmacology , University of Liverpool , Liverpool , UK.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Egan
authors.affiliation: b Department of Molecular & Clinical Pharmacology , University of Liverpool , Liverpool , UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Owen
authors.affiliation: d National Centre for HIV Oncology, Chelsea and Westminster Hospital , London , UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kelly
authors.affiliation: d National Centre for HIV Oncology, Chelsea and Westminster Hospital , London , UK.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Karolia
authors.affiliation: d National Centre for HIV Oncology, Chelsea and Westminster Hospital , London , UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Shaw
authors.affiliation: a Imperial College Faculty of Medicine , London , UK.|d National Centre for HIV Oncology, Chelsea and Westminster Hospital , London , UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bower
authors.affiliation: a Imperial College Faculty of Medicine , London , UK.|d National Centre for HIV Oncology, Chelsea and Westminster Hospital , London , UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D009154:Mutation; D012367:RNA, Viral; D019562:Viral Load
chemical_list: C000715087:ABCC2 protein, human; D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D012367:RNA, Viral
keywords: Antiretroviral therapy; Chemotherapy; HIV; Lymphoma