title: HIV viral kinetics and T cell dynamics in antiretroviral naïve persons starting an integrase strand transfer inhibitor and protease inhibitor regimen.
abstract: Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens may potentially minimize antiretroviral (ART) toxicities, but demonstrate mixed efficacy and toxicity results. The impact of an integrase strand transfer inhibitor (INSTI) and protease inhibitor (PI) regimen on HIV viral dynamics and T cell kinetics remains underdescribed.
  
  
  
  To compare the effect of raltegravir + ritonavir boosted lopinavir (RAL + LPV/r) to efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) on HIV kinetics and T cell dynamics.
  
  
  
  Fifty participants naïve to ART underwent HIV viral kinetic sampling evaluated using biexponential mixed effects modeling. A subset of 28 subjects (with complete viral suppression) underwent flow cytometry and evaluation of soluble markers of inflammation at weeks 0, 4, and 48 of ART.
  
  
  
  RAL + LPV/r compared to EFV/TDF/FTC resulted in a prolonged first phase viral decay rate (18 vs. 13 days p < 0.01). From weeks 0 to 4, RAL + LPV/r was associated with a trend toward greater decreases in activated CD4+T cells (-3.81 vs. -1.18 p = 0.09) and less decreases in activated effector memory CD4+T cells (-0.63 vs. -2.69 p-0.07). These trends did not persist to week 48. No differences were noted at any time point for soluble markers of immune activation.
  
  
  
  The prolonged first phase viral decay observed with RAL + LPV/r in persons starting ART did not result in differences in viral suppression at week 48. We also observed trends in declines in certain cellular markers of immune activation but it remains unclear if this could translate to long-term immunologic benefits in persons on an INSTI + PI.
authors.affiliation: a Department of Medicine , University California San Diego , San Diego , CA , USA.
authors.forename: Maile Y
authors.initials: MY
authors.lastname: Karris
authors.affiliation: b Department of Family and Preventive Medicine , University California San Diego , San Diego , CA , USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jain
authors.affiliation: c Department of Medicine , Washington University , Saint Louis , MO , USA.
authors.forename: Tyler R C
authors.initials: TR
authors.lastname: Day
authors.affiliation: a Department of Medicine , University California San Diego , San Diego , CA , USA.
authors.forename: Josué
authors.initials: J
authors.lastname: Pérez-Santiago
authors.affiliation: d Department of Medicine , Scripps Health San Diego , CA , USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Goicoechea
authors.affiliation: e Department of Medicine , University Southern California Keck School of Medicine , Los Angeles , CA , USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dubé
authors.affiliation: b Department of Family and Preventive Medicine , University California San Diego , San Diego , CA , USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Sun
authors.affiliation: f Department of Pathology , Veterans Affairs San Diego Healthcare System , San Diego , CA , USA.
authors.forename: Celsa
authors.initials: C
authors.lastname: Spina
authors.affiliation: g Los Angeles Biomedical Research Institute , Harbor-UCLA Medical Center , Los Angeles , CA , USA.|h David Geffen School of Medicine , UCLA , Los Angeles , CA , USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.affiliation: i Gilead Sciences , Forest city , CA , USA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Haubrich
authors.affiliation: a Department of Medicine , University California San Diego , San Diego , CA , USA.|b Department of Family and Preventive Medicine , University California San Diego , San Diego , CA , USA.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Morris
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D017320:HIV Protease Inhibitors
keywords: Antiretroviral naïve; CCTG 589; INSTI-PI regimen; Immune activation; NRTI sparing; T cell dynamics; Viral kinetics