title: Virological success of lopinavir/ritonavir salvage regimen is affected by an increasing number of lopinavir/ritonavir-related mutations.
abstract: We evaluated the virological outcome of lopinavir/ritonavir (LPV/RTV) in 224 HIV-1-infected and protease inhibitor (PI)-experienced patients showing virological failure to a highly active antiretroviral therapy (HAART) regimen and followed up for at least 3 months. At baseline, the median level of plasma viraemia was 4.61 log10 copies/ml (range 3-6.48) and the median CD4 cell count was 219 cells/mm3 (range 1-836). During a median follow-up of 272 days (range 92-635), we observed an increase in the number of CD4 cells (P=0.02) and a dramatic decrease in plasma viraemia levels (P=0.0001), which became undetectable in 122 patients (54.5%). The closely related predictive factors were baseline plasma viraemia levels and the number of mutations known to reduce susceptibility to LPV/RTV. Thirty-one patients (13.8%) discontinued LPV/RTV during the follow-up, and one AIDS event and three deaths were recorded. Of the 134 patients (59.8%) who underwent a baseline genotype resistance test, 22 (16.4%) had > or = 6 mutations known to reduce LPV/RTV susceptibility; plasma viraemia became undetectable in 76 patients (56.7%), only five of whom harboured > or = 6 mutations at baseline (P=0.0001). The independent predictive factors related to virological success were plasma viraemia levels and the number of mutations reducing susceptibility to LPV/RTV at baseline; each additional log10 copies/ml of HIV RNA reduced the probability of virological success by 34.0% and each extra mutation by 14.5%.
authors.affiliation: Institute of Infectious Diseases and Tropical Medicine, University of Milan, Italy. marco.bongiovanni@unimi.it
authors.forename: Marco
authors.initials: M
authors.lastname: Bongiovanni
authors.forename: Teresa
authors.initials: T
authors.lastname: Bini
authors.forename: Fulvio
authors.initials: F
authors.lastname: Adorni
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: Elisabetta
authors.initials: E
authors.lastname: Chiesa
authors.forename: Laura
authors.initials: L
authors.lastname: Cordier
authors.forename: Antonietta
authors.initials: A
authors.lastname: Cargnel
authors.forename: Simona
authors.initials: S
authors.lastname: Landonio
authors.forename: Stefano
authors.initials: S
authors.lastname: Rusconi
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D061466:Lopinavir; D008297:Male; D009154:Mutation / Q000235:genetics*; D016016:Proportional Hazards Models; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use*; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D014766:Viremia / Q000188:drug therapy
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir