Pilot Study of Effect of Kaletra on CD4 Response in HIV Positive (+) Patients With Viral Suppression KIMBO Study
To explore the hypothesis that the use of Lopinavir/ritonavir will be associated with improved CD4 immune reconstitution in volunteers who fail to demonstrate a significant CD4 cell increase (while on their first antiretroviral treatment regimen) despite sustained viral suppression by a non-Lopinavir/ritonavir-containing regimen
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Effect of Kaletra on CD4 Immune Reconstitution in HIV-infected Patients With Long-term Virologic Suppression on a Non-Kaletra Containing ART Regimen, But With a Blunted Immune Response|
- Absolute Change in CD4 Cell Count From Baseline, and at 6 and 12 Months [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
- Changes From Baseline in CD4 Cell Percentage at 6 and 12 Months [ Time Frame: Baseline, 6 and 12 months ] [ Designated as safety issue: No ]
- Changes From Baseline in CD4 Cell Count at 6 and 12 Months [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
- Baseline Will be Defined as the Mean of 2 Values Obtained Prior to the Medication Switch (for Analysis Purposes, the CD4 Cell Counts at 6 and 12 Months Will be Defined by the Mean of the CD4 Cell Counts Obtained at Months 3, 6 or 9, 12, Respectively). [ Time Frame: 3, 6, 0r 9, 12 months respectively ] [ Designated as safety issue: No ]
- Changes in the Slope of CD4 as Assessed 6 Months Prior to the Lopinavir/Ritonavir Switch (Baseline), Compared to 6-12 Month Intervals Post Initiation of Lopinavir/Ritonavir (Slope 1-6 Months, 1-12 Months) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||December 2005|
|Study Completion Date:||September 2009|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
Experimental: lopinavir/ritonavir (Kaletra)
lopinavir/ritonavir (Kaletra)400/100mg tablets by mouth twice a day for 48 weeks.
Dosing of Kaletra will be per package insert and BID with food. A three-drug standard of care antiretroviral regimen will be used in this study. Subjects will enter the study already on an effective, virally-suppressive treatment regimen. One of these drugs will be substituted for Lopinavir/ritonavir (Kaletra®). However, the nucleoside/nucleotide backbone drugs that the subject is already on will remain the same.
Other Name: Kaletra
This is an open-labeled, non-randomized exploratory trial in selected volunteers who meet the stated enrollment criteria. This study will assess the impact of Lopinavir/ritonavir on CD4 immune reconstitution. All volunteers must have been on antiretroviral therapy with sustained viral load suppression of < 400 copies/mL for at least 24 months (or, HIV-1 RNA < 400 copies/mL for 12 months, during which HIV-1 RNA was < 50 copies/mL for 6 months prior to screen). Despite induction of viral suppression, all volunteers must have demonstrated limited post-antiretroviral CD4 increase.
Lopinavir/ritonavir will be substituted for one of the 3 ARV drugs in the current (baseline) antiretroviral treatment regimen. Lopinavir/ritonavir will be substituted for any of the following: 3rd NRTI, an NNRTI, a PI or a boosted PI, while the nucleoside backbone will remain the same. If the subject is currently on a three-drug nucleoside/nucleotide plus a 4th anchor drug such as a NRTI, NNRTI, PI or boosted PI regimen, the triple nucleoside will remain constant and only the anchor drug is to be substituted with Lopinavir/ritonavir. Patients on 2 NRTIs with an NNRTI and a PI combination will not be allowed in the study.
Patients will be evaluated frequently, to include physical examination, assessment for the development of AIDS-defining conditions, hematology, chemistry, lipid profile, CD4 CD8 cell counts, plasma HIV-1 RNA ultrasensitive, and assessment of adverse events. If HIV-1 RNA becomes detectable, this will be repeated for confirmation with 2 weeks. HIV genotyping and phenotyping will be performed on patients who demonstrate repetitive plasma viral load levels of > 1,000 copies/mL.
An assessment of memory and naïve T cell response to antiretroviral regimen change will be performed in this study.
Dose and dose selection Lopinavir/ritonavir is also approved for once a day dosing. The dose of lopinavir/ritonavir (Kaletra) for this study will be 400/100mg. BID or 800/200mg. qd. New tablet formulation no longer requires that lopinavir/ritonavir be taken with food. We will give the volunteer the option for once a day dosing or BID dosing of Kaletra. However, those switching from an NNRTI to Kaletra will initially be placed on BID dosing of Kaletra, and allowed to switch to once-a-day dosing of Kaletra after 4 weeks on study drug.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00344487
|United States, Maryland|
|University of Maryland, Institute of Human Virology|
|Baltimore, Maryland, United States, 21201|
|Principal Investigator:||Charles E Davis, MD||University of Maryland, School of Medicine, Department of Infectious Disease|