title: Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens.
abstract: We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir-boosted protease inhibitor.
  
  
  
  Data from 206 drug-naïve and 327 PI-experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined.
  
  
  
  DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug-naïve and PI-experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug-naïve patients [>500 000 HIV-1 RNA copies/mL: median [interquartile range (IQR)] 6.1 (5.1-10.3) months; 100 000-500 000 copies/mL: median (IQR) 4.9 (3.8-6.1) months; <100 000 copies/mL: median (IQR) 3.9 (3.5-4.8) months; P < 0.001] and in PI-experienced patients [≥100 000 copies/mL: median (IQR) 7.2 (5.7-11.6) months; <100 000 copies/mL: median (IQR) 2.8 (2.4-3.3) months; P < 0.001]. In PI-experienced patients, the probability of VR was higher for higher viraemia levels (22.3% for ≥100 000 copies/ml vs. 9.7% for <100 000 copies/mL; P = 0.007). Baseline resistance did not affect the virological response. At failure, a high percentage of patients maintained virus susceptible to all PIs (drug-naïve: 95%; PI-experienced: 80%). Despite being used more often in patients with more complex requirements, DRV600 performed as well as DRV800.
  
  
  
  In clinical practice, use of DRV/r (with its flexible dosage) results in high rates of virological response. These data support the use of PI/r in patients whose characteristics require potent drugs with a high genetic barrier.
authors.affiliation: Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Armenia
authors.affiliation: Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Di Carlo
authors.affiliation: Infectious Diseases Division, University Hospital Tor Vergata, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Maffongelli
authors.affiliation: Infectious Diseases Division, Modena University Hospital, Modena, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Borghi
authors.affiliation: Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Alteri
authors.affiliation: Antiretroviral Therapy Monitoring Unit, L Spallanzani Hospital, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Forbici
authors.affiliation: Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.|Molecular Virology Division, University Hospital Tor Vergata, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bertoli
authors.affiliation: Antiretroviral Therapy Monitoring Unit, L Spallanzani Hospital, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gori
authors.affiliation: Infectious Dermatology Unit, San Gallicano Hospital, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Giuliani
authors.affiliation: Infectious Diseases Division, L Spallanzani Hospital, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Nicastri
authors.affiliation: Infectious Diseases Division, L Spallanzani Hospital, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zaccarelli
authors.affiliation: Infectious Diseases Division, L Spallanzani Hospital, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pinnetti
authors.affiliation: Infectious Diseases Division, L Spallanzani Hospital, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cicalini
authors.affiliation: Infectious Diseases Division, L Spallanzani Hospital, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: D'Offizi
authors.affiliation: Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.affiliation: Infectious Diseases Division, Modena University Hospital, Modena, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Mussini
authors.affiliation: Infectious Diseases Division, L Spallanzani Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Antinori
authors.affiliation: Infectious Diseases Division, University Hospital Tor Vergata, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Andreoni
authors.affiliation: Antiretroviral Therapy Monitoring Unit, L Spallanzani Hospital, Rome, Italy.
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
authors.affiliation: Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors.forename: M M
authors.initials: MM
authors.lastname: Santoro
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000069454:Darunavir / Q000008:administration & dosage*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019438:Ritonavir; D000069454:Darunavir
keywords: baseline viraemia; darunavir; darunavir dosage; drug resistance; virological response