title: Dual Raltegravir-Darunavir/Ritonavir Combination in Virologically Suppressed HIV-1-Infected Patients on Antiretroviral Therapy Including a Ritonavir-Boosted Protease Inhibitor Plus Two Nucleoside/Nucleotide Reverse Transcriptase Inhibitors.
abstract: BACKGROUND
  Nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapies may be useful in HIV-infected patients with resistance or intolerance to this class.
  
  
  METHODS
  We performed an observational study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted protease inhibitor who switched to a dual regimen containing raltegravir (400 mg twice daily) and darunavir/ritonavir (800/100 mg once daily) and were followed-up for 48 weeks.
  
  
  RESULTS
  As a whole, 82 patients were enrolled. Mean duration of current regimen was 4.6 years and mean duration of plasma HIV RNA < 50 copies/mL before the switch was 46.2 months. Reason for simplification was toxicity in 76 patients and resistance to NRTIs in 13. After switching, the percentage of patients with HIV RNA < 50 copies/mL at week 48 was 92.7% in the intent-to-treat-exposed analysis and 97.6% in the per-protocol analysis. The switch led to a significant reduction in the mean triglyceride value (-85.2 mg/dL), in the prevalence of tubular proteinuria (-56%) and in the mean level of interleukin-6 (-0.94 pg/mL), with a significant increase in the mean phosphoremia (+0.58 mg/dL). Mean trough concentrations of both raltegravir and darunavir were within the therapeutic range. Two patients (2.4%) had virological failure due to suboptimal adherence and 4 subjects (4.9%) discontinued treatment due to adverse events, but no patients experienced Grade 3 or 4 adverse events.
  
  
  CONCLUSIONS
  In our study, simplification to a dual therapy containing raltegravir plus darunavir/ritonavir after 48 weeks maintained viral suppression in more than 90% of patients and showed a good tolerability with a favourable effect on proteinuria, ipophosphoremia, and lipid metabolism.
authors.affiliation: 1 Department of Medical and Surgical Sciences, Clinics of Infectious Diseases, "Alma Mater Studiorum" University of Bologna, S. Orsola-Malpighi Hospital , Bologna, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Calza
authors.forename: Ilaria
authors.initials: I
authors.lastname: Danese
authors.forename: Eleonora
authors.initials: E
authors.lastname: Magistrelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Colangeli
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredi
authors.forename: Isabella
authors.initials: I
authors.lastname: Bon
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Re
authors.forename: Matteo
authors.initials: M
authors.lastname: Conti
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000145:classification* / Q000627:therapeutic use; D000069454:Darunavir / Q000008:administration & dosage / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D019438:Ritonavir; D000069454:Darunavir
keywords: darunavir; dual therapy; protease inhibitor; raltegravir; switch