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

NCT00051831 | Completed

• 3 other identifiers: A517310006ACTG A5173
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 7

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.

Conditions

HIV Infections

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Frequency of latently infected CD4+ T cells from peripheral blood with replication-competent HIV-1 (in infectious units per million cells)

  Throughout study

Secondary Outcomes (12)

• Any Grade 3 or 4 adverse experience, including Grade 3 or 4 laboratory value, sign or symptom, and all deaths.

  Throughout study

• Targeted events and toxicities will also be considered and these include injection site reactions (any grade), bacterial pneumonia, cellulitis

  Throughout study

• - Level of HIV-1 RNA in plasma as measured by the Roche Ultrasensitive assay

  Throughout study

• - Level of HIV-1 DNA in PBMC

  Throughout study

• - Frequency of 2-LTR in PBMC

  Throughout study

Study Arms (1)

1

EXPERIMENTAL

Drug: Emtricitabine; Drug: Enfuvirtide; Drug: Ritonavir; Drug: Saquinavir; Drug: Tenofovir disoproxil fumarate

Interventions

Emtricitabine DRUG

Will be administered as one 200-mg capsule orally daily

Also known as: FTC, Emtriva

1

Enfuvirtide DRUG

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

Also known as: ENF, Fuzeon, T-20

1

Ritonavir DRUG

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

Also known as: RTV, Norvir

1

Saquinavir DRUG

Will be administered as five hard gel capsules orally twice daily

Also known as: Invirase, Saquinavir mesylate

1

Tenofovir disoproxil fumarate DRUG

Will be administered as one 300-mg tablet orally daily

Also known as: TDF, Viread

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (7)

University of Colorado Hospital CRS

Aurora, Colorado, 80262-3706, United States

Location

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, 02114, United States

Location

Washington U CRS

St Louis, Missouri, 63108-2138, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016-6481, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27514, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Location

Puerto Rico-AIDS CRS

San Juan, 00936-5067, Puerto Rico

Location

Related Publications (5)

• Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557-93. doi: 10.1146/annurev.med.53.082901.104024.

  PMID: 11818490 BACKGROUND

• Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature. 1997 May 8;387(6629):188-91. doi: 10.1038/387188a0.

  PMID: 9144290 BACKGROUND

• Pierson T, McArthur J, Siliciano RF. Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu Rev Immunol. 2000;18:665-708. doi: 10.1146/annurev.immunol.18.1.665.

  PMID: 10837072 BACKGROUND

• Kilby JM, Hopkins S, Venetta TM, DiMassimo B, Cloud GA, Lee JY, Alldredge L, Hunter E, Lambert D, Bolognesi D, Matthews T, Johnson MR, Nowak MA, Shaw GM, Saag MS. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med. 1998 Nov;4(11):1302-7. doi: 10.1038/3293.

  PMID: 9809555 BACKGROUND

• Gandhi RT, Bosch RJ, Aga E, Albrecht M, Demeter LM, Dykes C, Bastow B, Para M, Lai J, Siliciano RF, Siliciano JD, Eron JJ; AIDS Clinical Trials Group A5173 Team. No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy. J Infect Dis. 2010 Jan 15;201(2):293-6. doi: 10.1086/649569.

  PMID: 20001856 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine; Enfuvirtide; Ritonavir; Saquinavir; Tenofovir

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; HIV Envelope Protein gp41; Viral Fusion Proteins; Membrane Fusion Proteins; Membrane Proteins; Proteins; HIV Antigens; Antigens, Viral; Viral Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins; Antigens; Biological Factors; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolines; Organophosphonates; Organophosphorus Compounds; Adenine; Purines

Study Officials

• Joseph J. Eron, Jr., MD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2003
• First Posted: January 20, 2003
• Study Start: October 1, 2003
• Primary Completion: December 1, 2007
• Study Completion: May 1, 2008
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (6); PR (1)