title: Open-label study of a twice-daily indinavir 800-mg/ritonavir 200-mg regimen in HIV-infected adults failing a protease inhibitor regimen.
abstract: There is no standard treatment of HIV-infected patients who fail protease inhibitor (PI)-containing antiretroviral therapy. This open-label, noncomparative 24-week study with a 24-week extension evaluated the efficacy, safety, and tolerability of twice-daily indinavir/ritonavir 800/200 mg plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) in this population. Presented here are the results of the 24-week study. Patients were HIV-infected adults who had prior viral RNA (vRNA) suppression (<400 copies/mL), subsequent failure (> or =400 and < or =100,000 copies/mL) on antiretroviral therapy, and at least one new NRTI available for treatment. The proportions of patients achieving plasma vRNA <400 and <50 copies/mL were analyzed with data as observed (DAO) and intention-to-treat (ITT) models using generalized estimating equations (GEE) or counting noncompleters as failures (NC = F). Mean changes from baseline in vRNA and CD4 cell count were evaluated using DAO and an ITT mixed-model approach. Sixty-three patients (87% male) with a mean age of 42 years and mean baseline vRNA and CD4 cell counts of 3.8 log(10) copies/mL and 360 cells/mm(3), respectively, were enrolled. The proportion (95% confidence interval) of patients achieving vRNA <400 and <50 copies/mL at week 24 were 76% (61%, 87%) and 50% (35%, 65%) for DAO, 64% (50%, 75%) and 43% (30%, 56%) for GEE, and 56% (43%, 68%) and 37% (25%, 50%) for NC = F, respectively. At Week 24, baseline vRNA decreased by >1.0 log(10) copies/mL and CD4 cell counts increased by approximately 90 cells/mm(3). Three patients (5%) experienced serious drug-related adverse events. Seven patients (11%) discontinued treatment due to clinical or laboratory adverse events. In this study, the enhanced, twice-daily regimen of indinavir/ritonavir 800/200 mg plus 2 NRTIs provided suppression of HIV in many patients who had failed a PI-containing regimen and was generally well tolerated.
authors.affiliation: Mercer University School of Medicine, Macon, Georgia, USA.
authors.forename: Harold P
authors.initials: HP
authors.lastname: Katner
authors.forename: David P
authors.initials: DP
authors.lastname: Paar
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Nadler
authors.forename: Erin H
authors.initials: EH
authors.lastname: Jensen
authors.forename: Helene M
authors.initials: HM
authors.lastname: Wilson
authors.forename: Tyler S
authors.initials: TS
authors.lastname: Finn
authors.forename: Richard A
authors.initials: RA
authors.lastname: Petruschke
authors.forename: Robert K
authors.initials: RK
authors.lastname: Zeldin
mesh_terms: D000138:Acidosis / Q000139:chemically induced; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000187:drug effects / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D006937:Hypercholesterolemia / Q000139:chemically induced; D006943:Hyperglycemia / Q000139:chemically induced; D015228:Hypertriglyceridemia / Q000139:chemically induced; D019469:Indinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D007669:Kidney Calculi / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019469:Indinavir; D019438:Ritonavir