Clinical Trials


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

This study has been completed
National Institute of Allergy and Infectious Diseases (NIAID)

AIDS Clinical Trials Group

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID) Identifier

First received: January 16, 2003
Last updated: May 29, 2015
Last Verified: May 2015
History of Changes


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
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

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 ]
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 ]
  • Targeted events and toxicities will also be considered and these include injection site reactions (any grade), bacterial pneumonia, cellulitis [ Time Frame: Throughout study ]
  • - Level of HIV-1 RNA in plasma as measured by the Roche Ultrasensitive assay [ Time Frame: Throughout study ]
  • - Level of HIV-1 DNA in PBMC [ Time Frame: Throughout study ]
  • - Frequency of 2-LTR in PBMC [ Time Frame: Throughout study ]
  • -Sequence of HIV env and HIV pol genes [ Time Frame: Throughout study ]
  • -CD8/CD38 antibody binding capacity (ABC) [ Time Frame: Throughout study ]
  • - Level of HIV-1 RNA in cerebrospinal fluid [ Time Frame: Throughout study ]
  • - Level of HIV-1 RNA in genital fluid [ Time Frame: Throughout study ]
  • - Level of HIV-1 RNA in plasma as measured by an ultra-ultrasensitive assay [ Time Frame: Throughout study ]
  • - Measures of cell surface density of chemokine (CCR5, CXCR5) receptors [ Time Frame: Throughout study ]
  • - Responses to subject preferences and injection administration concerns questionnaires [ Time Frame: Throughout study ]

Enrollment: 19
Study Start Date: October 2003
Study Completion Date: May 2008
Primary Completion Date: December 2007 (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 Name:
  • FTC
  • Emtriva

Drug: Enfuvirtide

Will be administered as a 90-mg (1.0 mL) subcutaneous injection twice daily

Other Name:
  • ENF
  • Fuzeon
  • T-20

Drug: Ritonavir

Will be administered as one 100-mg capsule orally twice daily

Other Name:
  • RTV
  • Norvir

Drug: Saquinavir

Will be administered as five hard gel capsules orally twice daily

Other Name:
  • Invirase
  • Saquinavir mesylate

Drug: Tenofovir disoproxil fumarate

Will be administered as one 300-mg tablet orally daily

Other Name:
  • 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.



Ages Eligible for Study: 18 Years and older  
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

contacts and locations

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 identifier: NCT00051831


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
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


Study Chair: Joseph J. Eron, Jr., MD University of North Carolina, Chapel Hill
More Information

More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00051831   History of Changes  
Other Study ID Numbers: A5173  
  ACTG A5173  
Study First Received: January 16, 2003  
Last Updated: May 29, 2015  

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:
HIV Infections
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