title: Use of lopinavir/ritonavir in HIV-infected patients failing a first-line protease-inhibitor-containing HAART.
abstract: OBJECTIVE
  The long-term virological efficacy of lopinavir/ritonavir-containing highly active antiretroviral therapy (HAART) in HIV-infected patients failing a first-line protease inhibitor (PI)-based regimen is still unclear.
  
  
  METHODS
  An observational study was carried out from December 2000-December 2002 on 111 consecutive patients starting lopinavir/ritonavir. The primary end-point was virological success (HIV RNA <50 copies/mL in two consecutive determinations). CD4 outcome, lipid levels and adverse events were recorded. The Kaplan-Meier method and log-rank test were used to estimate the time-dependent probability of reaching the end-point using intention-to-treat and on-treatment approaches.
  
  
  RESULTS
  Ninety-six patients obtained virological success during follow-up; Kaplan-Meier analysis showed that the time-dependent probability of obtaining this end-point was 78.4% at month 12 and 85.8% at month 24. The median CD4+cell count increased by 118 cells/mm(3) from baseline to month 12 and by 153 cells/mm(3) to month 24. Thirty-one patients discontinued lopinavir/ritonavir: 16 because of drug-related toxicities, six for simplification, five because of virological failure, one patient was lost at follow-up and three died. An elevation in lipid parameters was observed, but only a minority of patients developed a grade 3 or higher hypertriglyceridaemia and/or hypercholesterolaemia. Among the 15 patients not reaching virological success, five had < or =5 mutations in the protease region known to reduce susceptibility to lopinavir/ritonavir (one discontinued lopinavir/ritonavir because of gastrointestinal intolerance), five had no mutations (two discontinued lopinavir/ritonavir because of gastrointestinal intolerance) and five showed > or =6 mutations (all discontinued lopinavir/ritonavir); however, of the patients who discontinued lopinavir/ritonavir none achieved HIV RNA <50 copies/mL on subsequent regimens.
  
  
  CONCLUSIONS
  Lopinavir/ritonavir was highly effective and well tolerated in HIV-infected patients failing a first-line PI-based HAART.
authors.affiliation: Institute of Infectious and Tropical Diseases, Ospedale Luigi Sacco, University of Milan, Via G.B. Grassi 74, 20157 Milano, Italy. marco.bongiovanni@unimi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Bongiovanni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Chiesa
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.forename: Paola
authors.initials: P
authors.lastname: Meraviglia
authors.forename: Amedeo
authors.initials: A
authors.lastname: Capetti
authors.forename: Federica
authors.initials: F
authors.lastname: Tordato
authors.forename: Paola
authors.initials: P
authors.lastname: Cicconi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Biasi
authors.forename: Teresa
authors.initials: T
authors.lastname: Bini
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage*; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019438:Ritonavir