Pilot Study of Effect of Kaletra on CD4 Response in HIV Positive (+) Patients With Viral Suppression KIMBO Study

NCT00344487 | Terminated Results DMC

• 1 other identifier: H-27050
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

HIV

Outcome Measures

Primary Outcomes (4)

• Absolute Change in CD4 Cell Count From Baseline, and at 6 and 12 Months

  6 and 12 months

• Changes From Baseline in CD4 Cell Percentage at 6 and 12 Months

  Baseline, 6 and 12 months

• Changes From Baseline in CD4 Cell Count at 6 and 12 Months

  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).

  6 and 12 months

• Changes in Slope of CD4

  Changes in 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)

  6 and 12 months

Study Arms (1)

lopinavir/ritonavir (Kaletra)

EXPERIMENTAL

lopinavir/ritonavir (Kaletra)400/100mg tablets by mouth twice a day for 48 weeks.

Drug: Lopinavir/Ritonavir

Interventions

Lopinavir/Ritonavir DRUG

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.

Also known as: Kaletra

lopinavir/ritonavir (Kaletra)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Human Immunodeficiency Virus type-1 (HIV-1)infection, as documented by any licensed enzyme-linked immunosorbent assay ELISA)test kit, and confirmed by Western blot, positive HIV-1 blood culture, positive HIV serum antigen, or plasma viremia at any time prior to study entry. If no record exists, testing must occur at screening.
• Males and non-pregnant females \> 18 years of age.
• Currently on a stable antiretroviral regimen for at least 6 months prior to enrollment. This stable regimen must be their first treatment regimen, however, prior changes could have been made for toxicity or intolerability, or where providers were using an "induction /maintenance"type of treatment strategy.
• HIV-1 RNA \< 400 copies/ml (or \<500 copies/ml for the bDNA test or \<40 copies/ml for the nucleic acid sequence based amplification \[NASBA test\]) for at least 24 months; and an HIV-1 RNA \< 50 copies/ml at screening; interim, non-consecutive viral load blips of \< 1,000 copies/mL will be allowed
• Or, HIV-1 RNA \< 400 copies/ml (or \<500 copies/ml for the bDNA test or \<40 copies/ml for the NASBA test)for minimum of 12 months, during which the HIV-1 RNA was \< 50 copies/ml (or \<500 copies/ml for the bDNA test or \<40 copies/ml for the NASBA test) for 6 months prior to screening, and \< 50 copies/mL at screen
• At a minimum of twelve months post-initiation of antiretroviral therapy, CD4 count remains \< 200 cells/mm3, or if baseline CD4 count was between 200-300, and there is an increase of \< 50 cells/mm3 over a 12 month period.
• Laboratory tests within pre-specified limits
• Able to sign the informed consent, and is willing to comply with the requirements of this clinical trial.
• Available for at least 48 weeks of follow up.
• If female and of child bearing potential must consent to using at least two forms of contraception
• Participant must have a Primary Care Provider in order to be enrolled in this study.

You may not qualify if:

• Pregnant or breast-feeding woman
• Current treatment for malignancy other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or isolated cutaneous Kaposi's Sarcoma that is not being treated; those with prior cancer diagnosis, such as lymphomas must have been disease-free for at least 5 years
• Absolute neutrophil count \< 500, platelet count \< 50,000, hemoglobin \< 8 gm/dL
• Evidence of end-organ disease, defined as follows: renal (calculated creatinine clearance of less than 50 mL/min); liver (liver-associated enzymes \> 3 times the upper limits of normal)
• Grade 3 (ACTG Grading Scale) or higher cholesterol or triglyceride elevations
• Acute, serious infection requiring prescription drug therapy within 30 days prior to study entry
• In the opinion of the investigator, there is evidence of an active ongoing opportunistic infection
• Must not currently be undergoing treatment for an opportunistic infection.
• Use of immune stimulation agents known to impact CD4 cell count in the peripheral circulation, to include Interleukin 2 (IL2), interferon,Granulocyte Colony-Stimulating Factor(G-CSF),Granulocyte Macrophage Colony-stimulating Factor (GM-CSF), etc.
• Use of immune suppressive drugs.
• Subject is currently taking any of the following drugs: midazolam, triazolam, terfenadine, astemizole, cisapride, pimozide, propafenone, flecainide, certain ergot derivatives (ergotamine, dihydroergotamine, ergonovine, and methylergonovine), rifampin, lovastatin, simvastatin, St. John's Wort, doxorubicin, ribavirin, coumadin.
• Subject has significant history of cardiac, renal, neurologic, psychiatric, oncologic, endocrinologic (including diabetes mellitus), metabolic, or hepatic disease that would, in the opinion of the investigator, adversely affect his/her participation in this study.
• Unable or unwillingness to discontinue use of specific medications implicated in drug interactions while on Lopinavir/ritonavir
• Known hypersensitivity, allergic reactions, or intolerance to Lopinavir/ritonavir or to ritonavir in the past
• Have previously received Lopinavir/ritonavir for more than 3 months in the past

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland, Institute of Human Virology

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Interventions

Lopinavir; lopinavir-ritonavir drug combination

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

We screened and enrolled a total of three participants. Two of the three participants completed the study. Unable to meet the stated goals of the study, it was decided that it should be closed.

Results Point of Contact

• Title: Charles E. Davis, Jr. MD
• Organization: University of Maryland Institute of Human Virology

cdavis@ihv.umaryland.edu

410-706-1684

Study Officials

• Charles E Davis, MD

  University of Maryland, School of Medicine, Department of Infectious Disease

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 22, 2006
• First Posted: June 26, 2006
• Study Start: December 1, 2005
• Primary Completion: May 1, 2009
• Study Completion: September 1, 2009
• Last Updated: January 24, 2022
• Results First Posted: December 19, 2014

Record last verified: 2022-01

Locations

US (1)