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

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ClinicalTrials.gov Identifier: NCT00051831
Recruitment Status : Completed
First Posted : January 20, 2003
Last Update Posted : November 1, 2021
AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
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 or disease Intervention/treatment Phase
HIV Infections Drug: Emtricitabine Drug: Enfuvirtide Drug: Ritonavir Drug: Saquinavir Drug: Tenofovir disoproxil fumarate Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : October 2003
Actual Primary Completion Date : December 2007
Actual Study Completion Date : May 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Enfuvirtide

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Any Grade 3 or 4 adverse experience, including Grade 3 or 4 laboratory value, sign or symptom, and all deaths. [ Time Frame: Throughout study ]
  2. Targeted events and toxicities will also be considered and these include injection site reactions (any grade), bacterial pneumonia, cellulitis [ Time Frame: Throughout study ]
  3. - Level of HIV-1 RNA in plasma as measured by the Roche Ultrasensitive assay [ Time Frame: Throughout study ]
  4. - Level of HIV-1 DNA in PBMC [ Time Frame: Throughout study ]
  5. - Frequency of 2-LTR in PBMC [ Time Frame: Throughout study ]
  6. -Sequence of HIV env and HIV pol genes [ Time Frame: Throughout study ]
  7. -CD8/CD38 antibody binding capacity (ABC) [ Time Frame: Throughout study ]
  8. - Level of HIV-1 RNA in cerebrospinal fluid [ Time Frame: Throughout study ]
  9. - Level of HIV-1 RNA in genital fluid [ Time Frame: Throughout study ]
  10. - Level of HIV-1 RNA in plasma as measured by an ultra-ultrasensitive assay [ Time Frame: Throughout study ]
  11. - Measures of cell surface density of chemokine (CCR5, CXCR5) receptors [ Time Frame: Throughout study ]
  12. - Responses to subject preferences and injection administration concerns questionnaires [ Time Frame: Throughout study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00051831

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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
Saint Louis, Missouri, United States, 63108-2138
United States, New York
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
National Institute of Allergy and Infectious Diseases (NIAID)
AIDS Clinical Trials Group
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Study Chair: Joseph J. Eron, Jr., MD University of North Carolina, Chapel Hill
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00051831    
Other Study ID Numbers: A5173
10006 ( Registry Identifier: DAIDS ES )
ACTG A5173
First Posted: January 20, 2003    Key Record Dates
Last Update Posted: November 1, 2021
Last Verified: October 2021
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Naive
Virus Replication
CD4-Positive T-Lymphocytes
Immunologic Memory
Anti-HIV Agents
Drug Therapy, Combination
Tenofovir Disoproxil Fumarate
RNA, Viral
Viral Load
Fusion Inhibitors
Entry Inhibitors
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors