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A Research Study to See if a Change in Therapy for HIV Infection Can Improve the Immune Response to Treatment

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ClinicalTrials.gov Identifier: NCT00145795
Recruitment Status : Completed
First Posted : September 5, 2005
Results First Posted : August 27, 2013
Last Update Posted : August 27, 2013
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
David Pitrak, University of Chicago

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition HIV Infections
Interventions Drug: Kaletra + Current Dual NRTI Backbone
Drug: Current Regimen
Enrollment 20
Recruitment Details Patients were enrolled from the outpatient clinics at the University of Chicago and the University of Illinois, with approval from the Institutional Review Board at each institution.
Pre-assignment Details  
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone. Patients in this study arm continued their current regimen.
Period Title: Overall Study
Started 10 10
Completed 9 [1] 10
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
[1]
1 patient discontinued early due to grade II gastrointestinal symptoms.
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen Total
Hide Arm/Group Description Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone. Patients in this study arm continued their current regimen. Total of all reporting groups
Overall Number of Baseline Participants 10 10 20
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 10 participants 20 participants
45.5  (14.4) 40.5  (9.6) 43  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Female
2
  20.0%
1
  10.0%
3
  15.0%
Male
8
  80.0%
9
  90.0%
17
  85.0%
CD4 T cell count/mm^3  
Mean (Standard Deviation)
Unit of measure:  Number of cells per cubic mm
Number Analyzed 10 participants 10 participants 20 participants
172  (89) 264  (106) 218  (95.3)
Immune response at enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Nonresponder 5 5 10
Partial responder 5 5 10
Complete responder 0 0 0
[1]
Measure Description:

We grouped patients according to their baseline absolute CD4+ lymphocyte counts before the initiation of HAART as follows: group 1, CD4+ <100/mm3; group 2, 100–199/mm3; group 3, 200–399/mm3, group 4, 400–699/mm3; and group 5, >= 700/mm3.

Then, we categorized patients as complete or partial immune responders as follows. Complete immune responders have CD4+ counts increase to >700/mm3 after initiation of HAART. Partial immune responders have an increase in CD4+ count of >50% and improvement by at least one immunological grouping. All other patients are considered nonresponders.

Duration of HAART prior to study entry  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 10 participants 10 participants 20 participants
28.8  (23.4) 38.3  (28.8) 33.6  (25.5)
HAART regimen at enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Two NRTIs + NNRTI 7 6 13
Two NRTIs + PI 2 1 3
Two NRTIs + boosted PI 0 1 1
Three NRTIs 1 2 3
[1]
Measure Description: NRTI: nucleoside reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; PI: protease inhibitor; Boosted PI: Combine low-dose ritonavir with a second PI and two or more NRTIs
1.Primary Outcome
Title Immune Reconstitution [3 Months]
Hide Description Immune reconstitution is defined as the absolute CD4+ lymphocyte count after 3 months of therapy. Absolute CD4+ T cell count, our measure of immune recovery, was assessed in the clinical laboratory using fluorescent labeled monoclonal antibodies to the CD4 on lymphocytes. This is the main target cell for HIV infection. The absolute CD4+ T cell count is also the only clinically validated surrogate marker of immune dysfunction in HIV. CD4+ count is also our best predictor of morbidity and mortality outcomes.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: cells per cubic millimeter
41.56  (34.84) 49.40  (92.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Kaletra + Current Dual NRTI Backbone, Current Regimen
Comments Two-sample Student's t-test was used to examine the significance of the difference in mean absolute increase in CD4+ count at 3 months. Under the null hypothesis, CD4+ increase is similar for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments The significance level is 5%.
Method t-test, 2 sided
Comments This is a two-sample t-test assuming equal variances.
2.Primary Outcome
Title Immune Reconstitution [6 Months]
Hide Description Immune reconstitution is defined as the absolute CD4+ lymphocyte count after 6 months of therapy. Absolute CD4+ T cell count, our measure of immune recovery, was assessed in the clinical laboratory using fluorescent labeled monoclonal antibodies to the CD4 on lymphocytes. This is the main target cell for HIV infection. The absolute CD4+ T cell count is also the only clinically validated surrogate marker of immune dysfunction in HIV. CD4+ count is also our best predictor of morbidity and mortality outcomes.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: cells per cubic millimeter
116  (108) 32  (49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Kaletra + Current Dual NRTI Backbone, Current Regimen
Comments Two-sample Student's t-test was used to examine the significance of the difference in mean absolute increase in CD4+ count at 6 months. Under the null hypothesis, CD4+ increase is similar for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments Significance level is 5%.
Method t-test, 2 sided
Comments This is a two-sample t-test assuming equal variances.
3.Secondary Outcome
Title Rates of ex Vivo T Cell Apoptosis: CD4+ Memory Cell Population [3 Months]
Hide Description Ex vivo T cell apoptosis can be assessed many different ways. The use of propidium iodide staining to determine the proportion of isolated cells that have undergone apoptosis after ex vivo incubation is a standard method that has been used by many investigators. Apoptotic cells intercalate less PI into their DNA, and on flow cytometry, this cell population is identified by a decrease in mean fluorescence (shift to the left). We have experience with this assay, and we have published on the use of method for determining rates of ex vivo apoptosis for different immune effector cells.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: percent apoptosis
15.27  (6.99) 24.53  (13.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Kaletra + Current Dual NRTI Backbone, Current Regimen
Comments Two-sample Student's t-test was used to assess the difference in mean percent apoptosis for the CD4+ memory cell population at 3 months. Under the null hypothesis, percent CD4+ memory cell apoptosis is similar for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments The significance level is 5%.
Method t-test, 2 sided
Comments This is a two-sample t-test assuming equal variances.
4.Secondary Outcome
Title Rates of ex Vivo T Cell Apoptosis: CD4+ naïve Cell Population [3 Months]
Hide Description Ex vivo T cell apoptosis can be assessed many different ways. The use of propidium iodide staining to determine the proportion of isolated cells that have undergone apoptosis after ex vivo incubation is a standard method that has been used by many investigators. Apoptotic cells intercalate less PI into their DNA, and on flow cytometry, this cell population is identified by a decrease in mean fluorescence (shift to the left). We have experience with this assay, and we have published on the use of method for determining rates of ex vivo apoptosis for different immune effector cells.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: percent apoptosis
16.60  (9.62) 22.53  (13.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Kaletra + Current Dual NRTI Backbone, Current Regimen
Comments Two-sample Student's t-test was used to assess the difference in mean percent apoptosis for the CD4+ naïve cell population at 3 months. Under the null hypothesis, percent CD4+ naïve cell apoptosis is similar for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.29
Comments The significance level is 5%.
Method t-test, 2 sided
Comments This is a two-sample t-test assuming equal variances.
5.Secondary Outcome
Title Rates of ex Vivo T Cell Apoptosis: CD4+ Memory Cell Population [6 Months]
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: percent apoptosis
14.10  (5.53) 17.94  (9.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Kaletra + Current Dual NRTI Backbone, Current Regimen
Comments Two-sample Student's t-test was used to assess the difference in mean percent apoptosis for the CD4+ memory cell population at 6 months. Under the null hypothesis, percent CD4+ memory cell apoptosis is similar for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.29
Comments The significance level is 5%.
Method t-test, 2 sided
Comments This is a two-sample t-test assuming equal variances.
6.Secondary Outcome
Title Rates of ex Vivo T Cell Apoptosis: CD4+ naïve Cell Population [6 Months]
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: percent apoptosis
10.03  (5.25) 18.92  (10.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Kaletra + Current Dual NRTI Backbone, Current Regimen
Comments Two-sample Student's t-test was used to assess the difference in mean percent apoptosis for the CD4+ naïve cell population at 6 months. Under the null hypothesis, percent CD4+ naïve cell apoptosis is similar for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments The significance level is 5%.
Method t-test, 2 sided
Comments This is a two-sample t-test assuming equal variances.
7.Secondary Outcome
Title Rates of ex Vivo T Cell Apoptosis: CD8+ Cell Population [3 Months]
Hide Description [Not Specified]
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: percent apoptosis
20.92  (6.63) 16.74  (7.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Kaletra + Current Dual NRTI Backbone, Current Regimen
Comments Two-sample Student's t-test was used to assess the difference in mean percent apoptosis for the CD8+ cell population at 3 months. Under the null hypothesis, percent CD8+ cell apoptosis is similar for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.21
Comments The significance level is 5%.
Method t-test, 2 sided
Comments This is a two-sample t-test assuming equal variances.
8.Secondary Outcome
Title Rates of ex Vivo T Cell Apoptosis: CD8+ Cell Population [6 Months]
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: percent apoptosis
17.07  (9.38) 19.01  (6.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Kaletra + Current Dual NRTI Backbone, Current Regimen
Comments Two-sample Student's t-test was used to assess the difference in mean percent apoptosis for the CD8+ cell population at 6 months. Under the null hypothesis, percent CD8+ cell apoptosis is similar for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments The significance level is 5%.
Method t-test, 2 sided
Comments This is a two-sample t-test assuming equal variances.
9.Secondary Outcome
Title Clinical HIV-related Events
Hide Description Number of participants experiencing clinical HIV-related events as defined by category A, category B, and Appendix B in the "1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults" (http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm).
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Measure Type: Number
Unit of Measure: number of participants with event(s)
0 0
10.Secondary Outcome
Title Rates of Virologic Failure
Hide Description Virologic failure defined as HIV RNA > 2,000 copies/mL
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description:
Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.
Patients in this study arm continued their current regimen.
Overall Number of Participants Analyzed 9 10
Measure Type: Number
Unit of Measure: percentage of randomized subjects
0 0
Time Frame 0-6 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Kaletra + Current Dual NRTI Backbone Current Regimen
Hide Arm/Group Description Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone. Patients in this study arm continued their current regimen.
All-Cause Mortality
Kaletra + Current Dual NRTI Backbone Current Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Kaletra + Current Dual NRTI Backbone Current Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Kaletra + Current Dual NRTI Backbone Current Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   1/10 (10.00%)   0/10 (0.00%) 
Gastrointestinal disorders     
Nausea dyspepsia   1/10 (10.00%)  0/10 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. David Pitrak
Organization: The University of Chicago Department of Health Studies, Section of Infectious Diseases and Global Health
Phone: (773) 702-2710
EMail: dpitrak@medicine.bsd.uchicago.edu
Layout table for additonal information
Responsible Party: David Pitrak, University of Chicago
ClinicalTrials.gov Identifier: NCT00145795     History of Changes
Other Study ID Numbers: 11711B
First Submitted: September 1, 2005
First Posted: September 5, 2005
Results First Submitted: October 24, 2012
Results First Posted: August 27, 2013
Last Update Posted: August 27, 2013