A Phase 4 interventional study of Lopinavir 400 mg/ritonavir 100 mg and Efavirenz in Acquired Immune Deficiency Syndrome, sponsored by Rush University Medical Center. Terminated at 4 sites in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2023-05-26.
Sponsored by Rush University Medical Center · Phase 4, Interventional, and Treatment
The ideal anti-HIV medications for patients with advanced HIV disease is unknown. There is evidence that anti-HIV regimens that contain protease inhibitors can enhance immune function better than regimens that do not contain protease inhibitors. This is a study that will determine the difference in immune enhancement capabilities between an anti-HIV regimen that contains the protease inhibitor - lopinavir-ritonavir, and a regimen that contains efavirenz. Both medications are recommended as first line treatments for HIV-infected patients. This study will recruit HIV-positive patients that need to start anti-HIV treatment because their CD4+ T-cells are below 200. The usual threshold for starting treatment is a CD4+ T-cell less than 350. Subjects will be randomized to treatment with either an anti-HIV regimen that contains lopinavir-ritonavir or a regimen that contains efavirenz. The study will determine the difference in immune reconstitution over 24 weeks of treatment with study medications. Among the immune parameters that will be measured is the ability of each subject to respond to vaccination with the tetanus-diphtheria vaccine and the 23-valent pneumococcal vaccine. Both vaccines are also recommended for HIV-positive patients but HIV-positive patients tend to have a lower response rate to these vaccines.
DESIGN: ICE-001 is a phase IV, randomized, two-arm unblinded study, comparing the effect on immune reconstitution of open-label ritonavir (RTV)-enhanced lopinavir (LPV) to efavirenz (EFV), in combination with daily emtricitabine (FTC)/tenofovir (TDF) as initial therapy for HIV-1 infection in HIV-infected treatment naïve subjects with CD4+ T-cells less than 200 cells/ml.
DURATION: Subjects will participate in ICE-001 for approximately 48 weeks after starting study treatment.
SAMPLE SIZE: ICE-001 will enroll 60 subjects (30 per treatment arm).
POPULATION: HIV-1-infected, antiretroviral (ARV) drug-naïve (≤7 days of ARV treatment at anytime prior to study entry) men and women between18 to 60 years of age with plasma HIV-1 RNA levels >1000 copies/mL and CD4+ T-cell counts \< 200 cells/ml obtained within 90 days prior to study entry.
STRATIFICATION: Subjects will be stratified at screening based on plasma HIV-1 RNA levels \<100,000 and ≥100,000 copies/mL.
REGIMEN: At entry subjects will be randomized to one of the following:
The objective is to determine the differences in the degree of immune reconstitution in HIV-infected patients with a CD4+ T-cell count \< 200 cells/ml who initiated treatment with LPV/RTV + FTC/TDF compared to EFV/FTC/TDF.
Study visits will occur at screening, pre-entry, entry and weeks 1, 4, 8, 12, 24 and 48 after study entry. Study medications will be provided at entry after randomization. At most study visits, clinical assessments, including histories, physical exams and determination of drug adherence, will occur. Blood for hematologic and metabolic safety assessments and for the assessment of immune parameters will be obtained. Immune parameters that will be measured include levels of T-cell apoptosis, maturation and activation. Frequencies of various T-cell subsets and other lymphocyte populations will also be done. Response to vaccination with tetanus-diphtheria vaccine and 23-valent pneumococcal polysaccharide vaccine (both given at week 8) will be measured.
2,040 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 272 are open to participants now.
This study's enrollment of 15 is below the median of 105 across 1,543 interventional studies indexed under Acquired Immunodeficiency Syndrome.
Browse Acquired Immunodeficiency Syndrome studies →Rush University Medical Center is the lead sponsor of 394 studies on the registry; 61 are open to participants now.
Of its 30 completed or terminated interventional studies of FDA-regulated products, 25 (83%) have results posted.
Counted across the registry records on this site, refreshed daily.
Laboratory values obtained within 30 days prior to study entry.
Exclusion Criteria:
Subjects randomized to Arm A initiated Lopinavir 400 mg/ritonavir 100 mg BID + emtricitabine 200 mg/tenofovir 300 mg QD
Drug: Lopinavir 400 mg/ritonavir 100 mg
Subjects randomized to Arm B initiated Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD
Drug: Efavirenz
Lopinavir 400 mg/ritonavir 100 mg fixed dose combination BID + emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD
Also known as: Kaletra, Truvada
Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD
Also known as: Atripla
CD4+ (Cluster of Differentiation 4) T-cell Apoptosis
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.
Time frame: 24 weeks from treatment initiation (baseline and week 24)
CD4+ T-cell Change
This measures the change in CD4+ T-cells from baseline to week 24 of treatment.
Time frame: 24 weeks after treatment initiation (baseline and week 24)
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency
Naive, central memory, effector memory, and T reg CD4+ T-cell frequency at baseline
Time frame: baseline measurements
Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency
Naive, central memory and effector memory, and T reg CD4+ T-cell frequency at week 24
Time frame: week 24 measurements
Activation and Proliferation of CD4+ and CD8+ T-cell Frequencies
Activation and proliferation of CD4+ and CD8+ T cells were measured at baseline
Time frame: baseline measurements
Activated and Regulatory CD4+ and CD8+ T-cell Frequencies
Activation of CD4+ and CD8+ T cells were measured at week 24
Time frame: week 24 measurements
Response to Immunization With Pneumococcus Polysaccharide and Tetanus-diphtheria Vaccines
Response to immunization with pneumococcus polysaccharide and tetanus-diphtheria vaccines was not done due to small sample size
Time frame: 4 weeks after treatment initiation
| Milestone | ARM A/Lopinavir-ritonavir | ARM B/Efavirenz |
|---|---|---|
| Started | 8 | 5 |
| Completed | 5 | 5 |
| Not completed | 3 | 0 |
| Withdrew: Study sponsor terminated funding | 3 | 0 |
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.
| per cent | ARM A/Lopinavir-ritonavir | ARM B/Efavirenz |
|---|---|---|
| CD4+ (Cluster of Differentiation 4) T-cell Apoptosis | -12.33 ± 12.34 | -8.01 ± 7.97 |
This measures the change in CD4+ T-cells from baseline to week 24 of treatment.
| cells/mm3 | ARM A/Lopinavir-ritonavir | ARM B/Efavirenz |
|---|---|---|
| CD4+ T-cell Change | 176.83 ± 101.39 | 102.6 ± 150.45 |
Naive, central memory, effector memory, and T reg CD4+ T-cell frequency at baseline
| percentage of cells | ARM A Lopinavir/Ritonavir | ARM B Efavirenz |
|---|---|---|
| Mean percentage of naive CD4+ T cells at baseline | 32.67 (23.73 to 45.54) | 24.70 (1.66 to 38.54) |
| Mean percentage of central memory CD4+ T cells at baseline | 11.54 (5.09 to 16.43) | 9.02 (6.03 to 11.49) |
| Mean percentage of effector memory CD4+ T cells at baseline | 36.44 (24.86 to 46.3) | 47.32 (31.25 to 64.31) |
| Mean percentage of CD4+ Treg cells at baseline | 7.35 (1.46 to 16.87) | 6.96 (3.57 to 12.78) |
Naive, central memory and effector memory, and T reg CD4+ T-cell frequency at week 24
| percentage of cells | ARM A Lopinavir/Ritonavir | ARM B Efavirenz |
|---|---|---|
| Mean percentage of naive CD4+ T cells at week 24 | 29.08 (17.8 to 47.25) | 25.73 (1.82 to 49.13) |
| Mean percentage of central memory CD4+ T cells at week 24 | 10.89 (3.83 to 22.37) | 8.28 (5.48 to 11.03) |
| Mean percentage of effector memory CD4+ T cells at week 24 | 34.98 (24.37 to 43.37) | 44.82 (21.55 to 69.53) |
| Mean percentage of CD4+ Treg cells at week 24 | 5.58 (1.6 to 8.63) | 5.51 (4.7 to 6.52) |
Activation and proliferation of CD4+ and CD8+ T cells were measured at baseline
| percentage of cells | ARM A Lopinavir-ritonavir | ARM B Efavirenz |
|---|---|---|
| Activation of CD4+ T cells at baseline | 12.85 (4.52 to 16.11) | 12.35 (5.61 to 16.92) |
| Activation of CD8+ T cells at baseline | 34.61 (21.25 to 41.21) | 33.57 (11.36 to 59.10) |
| Proliferation of CD4+ T cells at baseline | 1.21 (0.73 to 2.11) | 1.25 (0.56 to 2.20) |
| Proliferation of CD8+ T cells at baseline | 1.39 (0.71 to 2.49) | 1.25 (0.58 to 2.41) |
Activation of CD4+ and CD8+ T cells were measured at week 24
| percentage of cells | ARM A Lopinavir-ritonavir | ARM B Efavirenz |
|---|---|---|
| Activation of CD4+ T cells at week 24 | 8.70 (3.42 to 12.39) | 7.39 (6.12 to 10.74) |
| Activation of CD8+ T cells at week 24 | 20.92 (6.72 to 29.97) | 17.17 (6.08 to 24.24) |
| Proliferation of CD4+ T cells at week 24 | 0.47 (0.25 to 0.68) | 0.52 (0.24 to 0.8) |
| Proliferation of CD8+ T cells at week 24 | 0.81 (0.21 to 3.08) | 0.48 (0.16 to 0.97) |
Response to immunization with pneumococcus polysaccharide and tetanus-diphtheria vaccines was not done due to small sample size
No measurements were reported for this outcome.
Collected over Week 24. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ARM A/Lopinavir-ritonavir | — | 0/8 (0%) | 1/8 (12.5%) |
| ARM B/Efavirenz | — | 0/5 (0%) | 0/5 (0%) |
| Event | ARM A/Lopinavir-ritonavir | ARM B/Efavirenz |
|---|---|---|
| Grade 3 elevation in ALTHepatobiliary disorders | 1/8 | 0/5 |
| Age, Categorical(Participants) | ARM A | ARM B | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 8 | 5 | 13 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | ARM A | ARM B | Total |
|---|---|---|---|
| Mean | 34.5 ± 9.4 | 30.6 ± 7.1 | 33 ± 8.5 |
| Sex: Female, Male(Participants) | ARM A | ARM B | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 8 | 5 | 13 |
| Region of Enrollment(participants) | ARM A | ARM B | Total |
|---|---|---|---|
| United States | 8 | 5 | 13 |
This study is terminated, as verified in May 2023. You cannot join it, but the record below documents what was studied.
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Acquired Immunodeficiency Syndrome→
Rush University Medical Center