title: Amprenavir in pre-treated patients: virological and immunological response in a cohort of 45 patients.
abstract: Treatment failure after preceding protease inhibitors (PI) is often due to resistance mutations. Our objective was to evaluate amprenavir (APV) in pre-treated patients and to correlate it with pre-existing mutations. - Fourty five patients were entered in an open label prospective study (6/99-12/2000). Pre-treatment was 6.2 years +/- 2.4 (2-11.3) and included a mean of 4.13 nucleosides (RTIs) and 2.73 PIs. Genotypic resistance testing was performed prior to the switch. APV dose was 1200 mg/d in combination with ritonavir (RTV) boosting (2 x 100mg) and 2 x 1200 mg/d in 6 patients without RTV. Co-medication was selected based on treatment history and results of genotypic testing. - The median duration of treatment at analysis was 34 weeks. Plasma viral load (VL) average at baseline was 4.6 log subset 10 +/- 08. After 24 weeks the mean VL reduction was 1.4 log subset 10 +/- 1.2 3.86-0.40s). A VL reduction of >1.5 log subset 10 was found in 16/45 patients (36%), 21/45 (47%) patients achieved a VL <400 cp/ml, and 12/45 (27%) a VL < 50 cp/ml. CD4 cells increased from a mean baseline of 208/microl +/- 185 to 318/microl +/- 253. Fourty percent (18/45) of patients had a CD4 gain of more than 100 cells/microl. Genotypic resistance determination showed PI mutations in 87% of patients tested. The average number of mutated codons was 4.54. Three of 4 patients with I84V mutation did not achieve an undetectable VL. - Our findings demonstrate that APV and APV/RTV plus two additional antiretrovirals has a good virological and immunological success rate in pre-treated patients. Presence of more than two APV resistance mutations was associated with treatment failure.
authors.affiliation: Department of Infectious Diseases, Medizinische Poliklinik, University Hospital of Munich, Germany. jobogner@pk-i.med.uni-muenchen.de
authors.forename: J R
authors.initials: JR
authors.lastname: Bogner
authors.forename: J
authors.initials: J
authors.lastname: Eberle
authors.forename: U
authors.initials: U
authors.lastname: Troendle
authors.forename: F-D
authors.initials: FD
authors.lastname: Goebel
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002219:Carbamates; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D005838:Genotype; D006678:HIV / Q000187:drug effects / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D019438:Ritonavir