title: The independent effect of drug resistance on T cell activation in HIV infection.
abstract: OBJECTIVE
  Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors.
  
  
  METHODS
  Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and antiretroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications.
  
  
  RESULTS
  Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease.
  
  
  CONCLUSIONS
  Antiretroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia.
authors.affiliation: Positive Health Program, San Francisco General Hospital, University of California, San Francisco, California 94110, USA. phunt@php.ucsf.edu
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: Andrew
authors.initials: A
authors.lastname: Moss
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Teri
authors.initials: T
authors.lastname: Liegler
authors.forename: Michael
authors.initials: M
authors.lastname: Bates
authors.forename: Gabriel
authors.initials: G
authors.lastname: Tsao
authors.forename: Harry
authors.initials: H
authors.lastname: Lampiris
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*; D014766:Viremia
chemical_list: D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D051997:ADP-ribosyl Cyclase 1