Trial Outcomes & Findings for Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease (NCT NCT00775606)

Results Overview

Change in the percentage of naive CD4 T-cells undergoing apoptosis as measured by propidium iodide staining. This is a lab test that measures the percentage of naive CD4 T-cells that are undergoing cell death. The change in this measure is obtained by determining the difference between the percentage of naive CD4 T-cells undergoing apoptosis at week 24 of treatment and the percentage undergoing apoptosis at baseline.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

15 participants

Primary outcome timeframe

24 weeks from treatment initiation (baseline and week 24)

Results posted on

2023-05-26

Participant Flow

Two subjects withdrew participation prior to starting study

Participant milestones

Participant milestones
Measure	ARM A/Lopinavir-ritonavir Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Overall Study STARTED	8	5
Overall Study COMPLETED	5	5
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	ARM A/Lopinavir-ritonavir Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Overall Study Study sponsor terminated funding	3	0

Baseline Characteristics

Immune Reconstitution of Lopinavir/Ritonavir-Based vs Efavirenz-based HAART in Advanced HIV Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ARM A n=8 Participants Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B n=5 Participants Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	34.5 years STANDARD_DEVIATION 9.4 • n=5 Participants	30.6 years STANDARD_DEVIATION 7.1 • n=7 Participants	33 years STANDARD_DEVIATION 8.5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks from treatment initiation (baseline and week 24)

Change in the percentage of naive CD4 T-cells undergoing apoptosis as measured by propidium iodide staining. This is a lab test that measures the percentage of naive CD4 T-cells that are undergoing cell death. The change in this measure is obtained by determining the difference between the percentage of naive CD4 T-cells undergoing apoptosis at week 24 of treatment and the percentage undergoing apoptosis at baseline.

Outcome measures

Outcome measures
Measure	ARM A/Lopinavir-ritonavir n=5 Participants Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz n=5 Participants Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
CD4+ (Cluster of Differentiation 4) T-cell Apoptosis	-12.33 per cent Standard Deviation 12.34	-8.01 per cent Standard Deviation 7.97

SECONDARY outcome

Timeframe: 24 weeks after treatment initiation (baseline and week 24)

This measures the change in CD4+ T-cells from baseline to week 24 of treatment.

Outcome measures

Outcome measures
Measure	ARM A/Lopinavir-ritonavir n=5 Participants Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz n=5 Participants Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
CD4+ T-cell Change	176.83 cells/mm3 Standard Deviation 101.39	102.6 cells/mm3 Standard Deviation 150.45

SECONDARY outcome

Timeframe: baseline measurements

Population: 11 subjects contributed to the baseline data (6 randomized to lopinavir/ritonavir and 5 randomized to efavirenz).

Naive, central memory, effector memory, and T reg CD4+ T-cell frequency at baseline

Outcome measures

Outcome measures
Measure	ARM A/Lopinavir-ritonavir n=6 Participants Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz n=5 Participants Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency Mean percentage of naive CD4+ T cells at baseline	32.67 percentage of cells Interval 23.73 to 45.54	24.70 percentage of cells Interval 1.66 to 38.54
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency Mean percentage of central memory CD4+ T cells at baseline	11.54 percentage of cells Interval 5.09 to 16.43	9.02 percentage of cells Interval 6.03 to 11.49
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency Mean percentage of effector memory CD4+ T cells at baseline	36.44 percentage of cells Interval 24.86 to 46.3	47.32 percentage of cells Interval 31.25 to 64.31
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency Mean percentage of CD4+ Treg cells at baseline	7.35 percentage of cells Interval 1.46 to 16.87	6.96 percentage of cells Interval 3.57 to 12.78

SECONDARY outcome

Timeframe: week 24 measurements

Population: 10 subjects contributed to the week 24 data (6 randomized to lopinavir/ritonavir and 4 randomized to efavirenz).

Naive, central memory and effector memory, and T reg CD4+ T-cell frequency at week 24

Outcome measures

Outcome measures
Measure	ARM A/Lopinavir-ritonavir n=6 Participants Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz n=4 Participants Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency Mean percentage of central memory CD4+ T cells at week 24	10.89 percentage of cells Interval 3.83 to 22.37	8.28 percentage of cells Interval 5.48 to 11.03
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency Mean percentage of effector memory CD4+ T cells at week 24	34.98 percentage of cells Interval 24.37 to 43.37	44.82 percentage of cells Interval 21.55 to 69.53
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency Mean percentage of naive CD4+ T cells at week 24	29.08 percentage of cells Interval 17.8 to 47.25	25.73 percentage of cells Interval 1.82 to 49.13
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency Mean percentage of CD4+ Treg cells at week 24	5.58 percentage of cells Interval 1.6 to 8.63	5.51 percentage of cells Interval 4.7 to 6.52

SECONDARY outcome

Timeframe: baseline measurements

Population: 11 subjects contributed to the baseline data (6 randomized to lopinavir/ritonavir and 5 randomized to efavirenz).

Activation and proliferation of CD4+ and CD8+ T cells were measured at baseline

Outcome measures

Outcome measures
Measure	ARM A/Lopinavir-ritonavir n=6 Participants Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz n=5 Participants Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Activation and Proliferation of CD4+ and CD8+ T-cell Frequencies Activation of CD8+ T cells at baseline	34.61 percentage of cells Interval 21.25 to 41.21	33.57 percentage of cells Interval 11.36 to 59.1
Activation and Proliferation of CD4+ and CD8+ T-cell Frequencies Proliferation of CD4+ T cells at baseline	1.21 percentage of cells Interval 0.73 to 2.11	1.25 percentage of cells Interval 0.56 to 2.2
Activation and Proliferation of CD4+ and CD8+ T-cell Frequencies Activation of CD4+ T cells at baseline	12.85 percentage of cells Interval 4.52 to 16.11	12.35 percentage of cells Interval 5.61 to 16.92
Activation and Proliferation of CD4+ and CD8+ T-cell Frequencies Proliferation of CD8+ T cells at baseline	1.39 percentage of cells Interval 0.71 to 2.49	1.25 percentage of cells Interval 0.58 to 2.41

SECONDARY outcome

Timeframe: week 24 measurements

Population: 10 subjects contributed to the week 24 data (6 randomized to lopinavir/ritonavir and 4 randomized to efavirenz).

Activation of CD4+ and CD8+ T cells were measured at week 24

Outcome measures

Outcome measures
Measure	ARM A/Lopinavir-ritonavir n=6 Participants Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz n=4 Participants Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Activated and Regulatory CD4+ and CD8+ T-cell Frequencies Activation of CD4+ T cells at week 24	8.70 percentage of cells Interval 3.42 to 12.39	7.39 percentage of cells Interval 6.12 to 10.74
Activated and Regulatory CD4+ and CD8+ T-cell Frequencies Activation of CD8+ T cells at week 24	20.92 percentage of cells Interval 6.72 to 29.97	17.17 percentage of cells Interval 6.08 to 24.24
Activated and Regulatory CD4+ and CD8+ T-cell Frequencies Proliferation of CD4+ T cells at week 24	0.47 percentage of cells Interval 0.25 to 0.68	0.52 percentage of cells Interval 0.24 to 0.8
Activated and Regulatory CD4+ and CD8+ T-cell Frequencies Proliferation of CD8+ T cells at week 24	0.81 percentage of cells Interval 0.21 to 3.08	0.48 percentage of cells Interval 0.16 to 0.97

SECONDARY outcome

Timeframe: 4 weeks after treatment initiation

Population: Response to PPSV23 and Td vaccines was not performed due to the small sample size.

Response to immunization with pneumococcus polysaccharide and tetanus-diphtheria vaccines was not done due to small sample size

Outcome measures

Outcome data not reported

Adverse Events

ARM A/Lopinavir-ritonavir

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

ARM B/Efavirenz

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	ARM A/Lopinavir-ritonavir n=8 participants at risk Subjects randomized to Arm a will initiate Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD	ARM B/Efavirenz n=5 participants at risk Subjects randomized to Arm B will initiate Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Hepatobiliary disorders Grade 3 elevation in ALT	12.5% 1/8 • Number of events 1 • Week 24	0.00% 0/5 • Week 24

Additional Information

Allan R. Tenorio

Rush University Medical Center

Phone: 312-942-3665

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place