Trial Outcomes & Findings for A Research Study to See if a Change in Therapy for HIV Infection Can Improve the Immune Response to Treatment (NCT NCT00145795)

NCT ID: NCT00145795

Last Updated: 2022-06-15

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 20 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2022-06-15

Participant Flow

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.

Participant milestones

Measure	Kaletra + Current Dual NRTI Backbone Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen Patients in this study arm continued their current regimen.
Overall Study STARTED	10	10
Overall Study COMPLETED	9	10
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Kaletra + Current Dual NRTI Backbone Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen Patients in this study arm continued their current regimen.
Overall Study Adverse Event	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Kaletra + Current Dual NRTI Backbone n=10 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.	Total n=20 Participants Total of all reporting groups
Age, Continuous	45.5 years STANDARD_DEVIATION 14.4 • n=5 Participants	40.5 years STANDARD_DEVIATION 9.6 • n=7 Participants	43 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
CD4 T cell count/mm^3	172 number of cells per cubic mm STANDARD_DEVIATION 89 • n=5 Participants	264 number of cells per cubic mm STANDARD_DEVIATION 106 • n=7 Participants	218 number of cells per cubic mm STANDARD_DEVIATION 95.3 • n=5 Participants
Immune response at enrollment Nonresponder	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Immune response at enrollment Partial responder	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Immune response at enrollment Complete responder	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Duration of HAART prior to study entry	28.8 months STANDARD_DEVIATION 23.4 • n=5 Participants	38.3 months STANDARD_DEVIATION 28.8 • n=7 Participants	33.6 months STANDARD_DEVIATION 25.5 • n=5 Participants
HAART regimen at enrollment Two NRTIs + NNRTI	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
HAART regimen at enrollment Two NRTIs + PI	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
HAART regimen at enrollment Two NRTIs + boosted PI	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
HAART regimen at enrollment Three NRTIs	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

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.

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Immune Reconstitution [3 Months]	41.56 cells per cubic millimeter Standard Deviation 34.84	49.40 cells per cubic millimeter Standard Deviation 92.41

PRIMARY outcome

Timeframe: 6 months

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.

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Immune Reconstitution [6 Months]	116 cells per cubic millimeter Standard Deviation 108	32 cells per cubic millimeter Standard Deviation 49

SECONDARY outcome

Timeframe: 3 months

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.

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Rates of ex Vivo T Cell Apoptosis: CD4+ Memory Cell Population [3 Months]	15.27 percent apoptosis Standard Deviation 6.99	24.53 percent apoptosis Standard Deviation 13.45

SECONDARY outcome

Timeframe: 3 months

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.

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Rates of ex Vivo T Cell Apoptosis: CD4+ naïve Cell Population [3 Months]	16.60 percent apoptosis Standard Deviation 9.62	22.53 percent apoptosis Standard Deviation 13.35

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Rates of ex Vivo T Cell Apoptosis: CD4+ Memory Cell Population [6 Months]	14.10 percent apoptosis Standard Deviation 5.53	17.94 percent apoptosis Standard Deviation 9.20

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Rates of ex Vivo T Cell Apoptosis: CD4+ naïve Cell Population [6 Months]	10.03 percent apoptosis Standard Deviation 5.25	18.92 percent apoptosis Standard Deviation 10.65

SECONDARY outcome

Timeframe: 3 months

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Rates of ex Vivo T Cell Apoptosis: CD8+ Cell Population [3 Months]	20.92 percent apoptosis Standard Deviation 6.63	16.74 percent apoptosis Standard Deviation 7.15

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Rates of ex Vivo T Cell Apoptosis: CD8+ Cell Population [6 Months]	17.07 percent apoptosis Standard Deviation 9.38	19.01 percent apoptosis Standard Deviation 6.99

SECONDARY outcome

Timeframe: 6 months

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).

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Clinical HIV-related Events	0 number of participants with event(s)	0 number of participants with event(s)

SECONDARY outcome

Timeframe: 6 months

Virologic failure defined as HIV RNA > 2,000 copies/mL

Outcome measures

Measure	Kaletra + Current Dual NRTI Backbone n=9 Participants Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 Participants Patients in this study arm continued their current regimen.
Rates of Virologic Failure	0 percentage of randomized subjects	0 percentage of randomized subjects

Adverse Events

Kaletra + Current Dual NRTI Backbone

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Current Regimen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Kaletra + Current Dual NRTI Backbone n=10 participants at risk Patients in this arm received Kaletra in addition to their current Dual NRTI Backbone.	Current Regimen n=10 participants at risk Patients in this study arm continued their current regimen.
Gastrointestinal disorders Nausea dyspepsia	10.0% 1/10 • 0-6 months	0.00% 0/10 • 0-6 months

Additional Information

Dr. David Pitrak

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

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place