title: Impact of reduced dosing of lopinavir/ritonavir in virologically controlled HIV-infected patients: the Kaledose trial.
abstract: BACKGROUND
  It is debated whether a risk of protease inhibitor mutation selection in proviral DNA exists during intermittent HIV-1 viraemia thereby impacting long-term virological control.
  
  
  METHODS
  Virologically controlled patients treated with lopinavir/ritonavir were included in a 48 week pilot trial during which lopinavir/ritonavir dosage was reduced if lopinavir concentration was >5000 ng/mL at inclusion. Serum lipids were longitudinally assessed and proviral DNA was quantified and sequenced in patients experiencing transient viraemia.
  
  
  RESULTS
  Thirty-three virologically suppressed patients while on a lopinavir/ritonavir-containing regimen were included, of whom 28 [20 males, mean age 44.6 years (SD 10.9)] completed the 48 week follow-up as scheduled. A significant decrease in lopinavir level was noted [mean C(min), 7363 ng/mL (min, 5118; max, 12 415) at baseline versus 4319 ng/mL (min, 1427; max, 8683) at week 48, P < 0.03]. A significant decrease in triglycerides was also observed [1.73 mmol/L (SD 1.08) at baseline versus 1.34 mmol/L (SD 0.91) at week 48, P = 0.03], whereas no significant change occurred for total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. In the 15 patients with transient viraemia, analysis of proviral DNA for antiretroviral resistance showed that mutations had occurred when compared with baseline genotypes in three patients: I47M (n = 2) and M46I (n = 1). Selection of these mutations was not associated with virological failure as all three patients had a sustained virological response without treatment modification after a 3 year follow-up.
  
  
  CONCLUSIONS
  This pilot study evaluating the biochemical and virological impact of a reduced dosing of lopinavir/ritonavir suggests that lower exposure to lopinavir/ritonavir could be associated with a significant decrease in triglycerides during treatment, without occurrence of resistance mutations that might impact the virological response to treatment.
authors.affiliation: Hôpital Saint-Antoine, AP-HP, Paris, France. jean-luc.meynard@sat.ap-hop-paris.fr
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Meynard
authors.forename: Laurence
authors.initials: L
authors.lastname: Morand-Joubert
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Poirier
authors.forename: Laurence
authors.initials: L
authors.lastname: Slama
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000302:isolation & purification; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008055:Lipids / Q000097:blood; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000302:isolation & purification; D011744:Pyrimidinones / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage*; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D008055:Lipids; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir