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

NCT00775606 | Terminated Phase 4 Results

• 1 other identifier: ICE-001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Acquired Immune Deficiency Syndrome

Keywords

AIDS, HIV

Outcome Measures

Primary Outcomes (1)

• 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.

  24 weeks from treatment initiation (baseline and week 24)

Secondary Outcomes (6)

• CD4+ T-cell Change

  24 weeks after treatment initiation (baseline and week 24)

• Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency

  baseline measurements

• Naive, Central Memory, Effector Memory, and T Reg CD4+ T-cell Frequency

  week 24 measurements

• Activation and Proliferation of CD4+ and CD8+ T-cell Frequencies

  baseline measurements

• Activated and Regulatory CD4+ and CD8+ T-cell Frequencies

  week 24 measurements

Study Arms (2)

ARM A/Lopinavir/ritonavir

ACTIVE COMPARATOR

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

ARM B/Efavirenz

ACTIVE COMPARATOR

Subjects randomized to Arm B initiated Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg QD

Drug: Efavirenz

Interventions

Lopinavir 400 mg/ritonavir 100 mg DRUG

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

ARM A/Lopinavir/ritonavir

Efavirenz DRUG

Efavirenz 600 mg/emtricitabine 200 mg/tenofovir 300 mg fixed dose combination QD

Also known as: Atripla

ARM B/Efavirenz

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV-1 infection
• Antiretroviral (ARV) drug-naïve
• Screening HIV-1 RNA \>1000 copies/mL
• Screening CD4+ T-cell count \< 200 cells/ml
• Laboratory values obtained within 30 days prior to study entry.
• Absolute neutrophil count (ANC) \>500/mm3
• Hemoglobin \>8.0 g/dL
• Platelet count \>40,000/mm3
• AST (SGOT), ALT (SGPT), and alkaline phosphatase \<5 x ULN
• Total bilirubin \<2.5 x ULN
• Calculated creatinine clearance ≥60 mL/min (by Cockcroft-Gault equation)
• For women of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to initiating study medications.
• Contraception requirements
• Men and women age \>18 years and \< 60 years.
• Ability and willingness of subject or legal guardian/representative to give written informed consent.

You may not qualify if:

• Currently breast-feeding.
• Use of immunomodulators, vaccines, growth hormone, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
• Known allergy/sensitivity to study drugs, pneumococcal polysaccharide vaccine, tetanus-diphtheria vaccine
• Receipt of pneumococcal polysaccharide vaccine or tetanus-diphtheria vaccine in the past 5 years.
• Active drug or alcohol use or dependence
• Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 14 days prior to study entry.
• Requirement for any current medications that are prohibited with any study treatment.
• Evidence of any major resistance-associated mutation on any genotype or evidence of significant resistance on any phenotype performed at any time prior to study entry
• Current or anticipated imprisonment or involuntary incarceration in a medical facility for psychiatric or physical (e.g., infectious disease) illness
• History of, or current bipolar disorder, major depression, schizophrenia or other psychotic disorders

Sponsors & Collaborators

• Rush University Medical Center: lead
• University of Chicago: collaborator
• University of Illinois at Chicago: collaborator
• Ruth M. Rothstein CORE Center: collaborator
• Abbott: collaborator
• Gilead Sciences: collaborator

Study Sites (4)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois Medical Center

Chicago, Illinois, 60612, United States

Location

Howard Brown Health Center

Chicago, Illinois, 60613, United States

Location

University of Chicago Hospital

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Pitrak DL, Novak RM, Estes R, Tschampa J, Abaya CD, Martinson J, Bradley K, Tenorio AR, Landay AL. Short communication: Apoptosis pathways in HIV-1-infected patients before and after highly active antiretroviral therapy: relevance to immune recovery. AIDS Res Hum Retroviruses. 2015 Feb;31(2):208-16. doi: 10.1089/aid.2014.0038. Epub 2014 Nov 11.

  PMID: 25386736 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Lopinavir; Ritonavir; lopinavir-ritonavir drug combination; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; efavirenz; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Tenofovir; Organophosphonates; Organophosphorus Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Oxazines

Limitations and Caveats

Study was terminated due to the slow recruitment and the small number of subjects.

Results Point of Contact

• Title: Allan R. Tenorio
• Organization: Rush University Medical Center

allan_s_tenorio@rush.edu

312-942-3665

Study Officials

• Allan R. Tenorio, M.D.

  Rush University Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 17, 2008
• First Posted: October 20, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2011
• Last Updated: May 26, 2023
• Results First Posted: May 29, 2014

Record last verified: 2023-05

Locations

US (4)