Study of the 48-Week Virologic and Immunologic Response to Lopinavir/Ritonavir (Kaletra) in HIV Positive Adult Patients

Summary

Expected Enrollment: 40 patients Study Start Date: June 2005 Study Objectives: * To conduct a pilot study to assess the safety, tolerability, and antiviral activity of Kaletra 400/100 mg taken twice a day (bid) in antiretroviral (ARV)-naïve HIV-infected patients at Week 48 Primary Objectives: * To determine the proportion of patients with HIV RNA \<400 copies/mL at weeks 24 and 48 * To determine the proportion of patients with HIV RNA \< 50 at weeks 24 and 48 * To elucidate the specific adverse event (AE) profile of Kaletra single agent therapy Secondary Objectives: * To assess the proportion of patients below the limit of quantification (LOQ) at each visit. Patients will be observed at baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48. * To determine the time to HIV RNA reaching \<400 and \<50 copies/mL * To determine the time to virologic failure * To assess change from baseline at each visit for HIV RNA and CD4 count at weeks 4, 8, 12, 24 and 48. * To assess changes in genotype from baseline to time of confirmed virologic failure (2 consecutive HIV RNA measurements \>400 copies/mL after suppressing to \<400 copies/mL) or at time of treatment intensification. * To characterize changes in lipid and triglyceride concentrations over time and the effect of treatment with appropriate drugs (fibrate or statin, if necessary) on these elevations. * To evaluate the safety and tolerability of subjects through 48 weeks of drug exposure. * To describe virologic response following intensification in Kaletra single agent virologic failures

Timeline

Start

2005-06

Primary completion

—

Completion

2007-12

Publications

• Background Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, d'Arminio Monforte A, Yust I, Bruun JN, Phillips AN, Lundgren JD. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet. 1998 Nov 28;352(9142):1725-30. doi: 10.1016/s0140-6736(98)03201-2.
• Background Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.
• Background Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J, Stryker R, Johnson P, Labriola DF, Farina D, Manion DJ, Ruiz NM. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med. 1999 Dec 16;341(25):1865-73. doi: 10.1056/NEJM199912163412501.
• Background Kaletra® (lopinavir/ritonavir) capsules-Complete Product Information
• Background Information for Clinical Investigators: Lopinavir (Abbott-157378) V 7.0
• Background Kempf et al. Seville 2002
• Background Stevens, et al. SOKRATES: Prospective Clinical Trials to Investigate the Evolution of Protease Resistance During Lopinavir/r Treatment. 2003. 1st European Drug Resistance Workshop, Luxemburg
• Background Allavena et al. Lopinavir/ritonavir-Efavirenz (LPV/r-EFV) NRTI-sparing Regimen (BIKS study): Preliminary Efficacy and Safety Data. 42nd ICAAC, San Diego 2002, #H-169
• Background Lauenroth-Mai & Schuler. Nuc-sparing salvage therapy: Immunological and virological response to a combination of indinavir (IDV) and lopinavir/ritonavir (LPV/r) in intensively pretreated HIV-infected patients with multiple NRTI resistance mutations. 6th IWDTHI, Glasgow 2002.
• Background Gathe et al. Pilot Study of the Safety and Efficacy of Lopinavir/Ritonavir (LPV/r) as Single Agent Therapy in HIV-1 ARV Naïve Patients. 44th Annual ICAAC, Washington, DC 2004.
• Background Pierone et al. Initial clinical experience with Kaletra (LPV/r) single agent therapy in HIV infection. 2002. HIV DART; Poster 076
• Background Pierone et al. Genotypic and phenotypic resistance observations among patients with viremia with on lopinavir/ritonavir "monotherapy". 44th Annual ICAAC, Washington, DC 2004.

Drugs

Indications