Effect of an Enfuvirtide-based Anti-HIV Drug Regimen on Latent HIV Reservoirs in Treatment Naive Adults

This study has been completed.
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00051831
First received: January 16, 2003
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

HIV replication in resting CD4 cells is so minimal that anti-HIV drugs often fail to destroy the virus in these cells. Enfuvirtide, also known as T-20, is a type of anti-HIV drug called a fusion inhibitor. The purpose of this study is to test the ability of a T-20-enhanced treatment regimen to decrease the number of resting CD4 cells that become infected with HIV.


Condition Intervention
HIV Infections
Drug: Emtricitabine
Drug: Enfuvirtide
Drug: Ritonavir
Drug: Saquinavir
Drug: Tenofovir disoproxil fumarate

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study to Measure the Clearance of Replication-Competent HIV-1 in Resting Memory CD4+ Cells in HIV-1-Infected Subjects Who Receive Enfuvirtide Plus Oral Combination Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency of latently infected CD4+ T cells from peripheral blood with replication-competent HIV-1 (in infectious units per million cells) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Any Grade 3 or 4 adverse experience, including Grade 3 or 4 laboratory value, sign or symptom, and all deaths. [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Targeted events and toxicities will also be considered and these include injection site reactions (any grade), bacterial pneumonia, cellulitis [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • - Level of HIV-1 RNA in plasma as measured by the Roche Ultrasensitive assay [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • - Level of HIV-1 DNA in PBMC [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • - Frequency of 2-LTR in PBMC [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • -Sequence of HIV env and HIV pol genes [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • -CD8/CD38 antibody binding capacity (ABC) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • - Level of HIV-1 RNA in cerebrospinal fluid [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • - Level of HIV-1 RNA in genital fluid [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • - Level of HIV-1 RNA in plasma as measured by an ultra-ultrasensitive assay [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • - Measures of cell surface density of chemokine (CCR5, CXCR5) receptors [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • - Responses to subject preferences and injection administration concerns questionnaires [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: October 2003
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Emtricitabine
Will be administered as one 200-mg capsule orally daily
Other Names:
  • FTC
  • Emtriva
Drug: Enfuvirtide
Will be administered as a 90-mg (1.0 mL) subcutaneous injection twice daily
Other Names:
  • ENF
  • Fuzeon
  • T-20
Drug: Ritonavir
Will be administered as one 100-mg capsule orally twice daily
Other Names:
  • RTV
  • Norvir
Drug: Saquinavir
Will be administered as five hard gel capsules orally twice daily
Other Names:
  • Invirase
  • Saquinavir mesylate
Drug: Tenofovir disoproxil fumarate
Will be administered as one 300-mg tablet orally daily
Other Names:
  • TDF
  • Viread

Detailed Description:

While current HIV treatment with combination antiretroviral therapy (ART) has reduced morbidity and mortality, it does not eradicate or cure HIV infection. A possible explanation for this failure is the persistence of virus in long-lived reservoirs. Resting memory CD4 cells have been proposed as providing a cellular reservoir. Most patients who initiate ART during chronic HIV-1 infection do not experience a detectable reduction in HIV in the latent reservoir; this may be due to low levels of ongoing viral replication that maintains the resting CD4 cell reservoir. Increasing the potency of therapy by inhibiting new viral targets may result in a decrease in the number of latently infected cells and clearance of the latent reservoir. Addition of the fusion inhibitor T-20 to ART including reverse transcriptase inhibitors and protease inhibitors (PIs) may help achieve this goal. This study will evaluate whether treatment naive, chronically infected HIV patients treated with T-20 plus emtricitabine (FTC), ritonavir (RTV), saquinavir (SQV), and tenofovir disoproxil fumarate (TDF) have a measurable decline in the latently infected CD4 cell reservoir. Patients and their physicians may choose different PIs than RTV and SQV, but they will not be provided by the study.

Patients in this study will receive injections of T-20 twice daily in addition to oral FTC and TDF once daily and oral RTV and SQV twice daily. At Week 24, patients will have their latent cell reservoir sampled. Patients whose HIV viral loads are less than 50 copies/ml at or after Week 24 but prior to Week 48 will continue the treatment regimen through the end of the study; their latent cell reservoirs will be tested at Weeks 48, 72, and 96. Patients whose viral loads are between 50 copies/ml and 200 copies/ml will continue the treatment regimen and latent cell sampling, but their regimens may be intensified as determined by the study team. Patients whose viral loads are 200 copies/ml or greater after Week 24 may continue their study regimens, but will no longer contribute latent cell samples.

This study will last 96 weeks. During the first 4 months of the study, patients will have 7 study visits; after that, study visits will be every 8 weeks until the end of the study. Medical history, clinical assessments, and blood collection will occur at every study visit. Pill and ENF vial counts will be assessed, and patients will be asked to complete a medication adherence questionnaire at selected study visits.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • HIV-1 infected
  • Viral load of 1,000 copies/ml or greater within 60 days prior to study entry
  • CD4 count of 100 cells/mm3 or greater within 60 days prior to study entry
  • Willing to use acceptable methods of contraception

Exclusion Criteria

  • Previous treatment with any nucleoside analogue, nonnucleoside reverse transcriptase inhibitor, or fusion inhibitor for longer than 7 days
  • Any previous treatment with T-20, lamivudine, or FTC
  • HIV-related vaccine within 6 months prior to study entry
  • Evidence of HIV seroconversion within 6 months prior to study entry
  • Acute AIDS-defining opportunistic infection (OI). Patients who are not clinically stable or who have not been on therapy for the OI for at least 30 days prior to study entry are excluded. Patients who have no evidence of active disease and have been receiving maintenance therapy for AIDS-related OI for at least 30 days are not excluded.
  • Systemic chemotherapy within 30 days of study entry or anticipated need for systemic chemotherapy before the end of the study
  • Treatment with immune modulators such as systemic steroids, IL-2, alpha interferon, G-CSF, erythropoietin, or any investigational agent within 30 days of study entry
  • Allergy to study drugs or their formulations
  • Serious illness, substance abuse, or other medical condition that would compromise the patient's ability to participate in the study
  • Certain primary resistance HIV mutations
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00051831

Locations
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262-3706
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States, 63108-2138
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016-6481
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27514
United States, Ohio
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
Puerto Rico
Puerto Rico-AIDS CRS
San Juan, Puerto Rico, 00936-5067
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Joseph J. Eron, Jr., MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00051831     History of Changes
Other Study ID Numbers: A5173, 10006, ACTG A5173
Study First Received: January 16, 2003
Last Updated: November 19, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Naive
HIV-1
Virus Replication
CD4-Positive T-Lymphocytes
Immunologic Memory
Pentafuside
Anti-HIV Agents
Drug Therapy, Combination
Saquinavir
Ritonavir
Tenofovir Disoproxil Fumarate
RNA, Viral
Viral Load
Fusion Inhibitors
Entry Inhibitors

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Saquinavir
Ritonavir
Enfuvirtide
Tenofovir
Tenofovir disoproxil
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Fusion Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014