title: Reduced immune activation during tenofovir-emtricitabine therapy in HIV-negative individuals.
abstract: BACKGROUND
  Elevated immune activation is associated with an increased risk of HIV acquisition. Tenofovir (TFV) has immunomodulatory properties in vitro, but how this extends in vivo remains unknown.
  
  
  METHODS
  HIV-negative adults received daily coformulated TFV disoproxil fumarate 300 mg/emtricitabine (FTC) 200 mg for 30 days followed by a 30-day washout. Markers of T-cell activation, inflammation, and cytokines were measured before drug and on days 30 (on drug) and 60 (30-day washout). Data were analyzed using one-way analysis of variance/pairwise comparisons. Intracellular disposition of TFV-diphosphate and FTC-triphosphate in CD4 and CD8 T-cells and monocytes was characterized, and the relationship with immune activation was evaluated using Pearson's correlation coefficient.
  
  
  RESULTS
  T-cell activation was available in 19 participants. CD38/HLA-DR coexpression on CD8 T-cells decreased from baseline to day 30 (3.97% vs. 2.71%; P = 0.03) and day 60 (3.97% vs. 2.41%; P = 0.008). Soluble CD27 decreased from baseline to day 60 (184.1 vs. 168.4 pg/mL; P = 0.001). Cytokines and inflammation markers were not significantly different. TFV-diphosphate and FTC-triphosphate were approximately 4-fold higher in monocytes vs. CD4 and CD8 T-cells but neither correlated with activation markers.
  
  
  CONCLUSIONS
  TFV disoproxil fumarate/FTC therapy was associated with decreased T-cell activation in HIV-negative adults, which could contribute to the antiviral effect of pre-exposure prophylaxis (NCT01040091; www.clinicaltrials.gov).
authors.affiliation: *Department of Medicine, Division of Infectious Diseases, School of Medicine, University of Colorado AMC, Aurora, CO; †Beacon Center for Infectious Disease, Boulder, CO; ‡Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado AMC, Aurora, CO; §Department of Medicine, Division of Allergy and Clinical Immunology, School of Medicine, University of Colorado AMC, Aurora CO; ‖Department of Medicine, Denver Health Medical Center, Denver, CO; and ¶Department of Biostatistics and Bioinformatics, Colorado School of Public Health, University of Colorado-AMC, Aurora, CO.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Castillo-Mancilla
authors.forename: Amie
authors.initials: A
authors.lastname: Meditz
authors.forename: Cara
authors.initials: C
authors.lastname: Wilson
authors.forename: Jia-Hua
authors.initials: JH
authors.lastname: Zheng
authors.forename: Brent E
authors.initials: BE
authors.lastname: Palmer
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lee
authors.forename: Edward M
authors.initials: EM
authors.lastname: Gardner
authors.forename: Sharon
authors.initials: S
authors.lastname: Seifert
authors.forename: Becky
authors.initials: B
authors.lastname: Kerr
authors.forename: Lane R
authors.initials: LR
authors.lastname: Bushman
authors.forename: Samantha
authors.initials: S
authors.lastname: MaWhinney
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068679:Emtricitabine; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage*; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D007155:Immunologic Factors; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine