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

NCT ID: NCT00051831

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-31
• Study Completion Date: 2008-05-31

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.

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Emtricitabine

Intervention Type: DRUG

Will be administered as one 200-mg capsule orally daily

Enfuvirtide

Intervention Type: DRUG

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

Ritonavir

Intervention Type: DRUG

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

Saquinavir

Intervention Type: DRUG

Will be administered as five hard gel capsules orally twice daily

Tenofovir disoproxil fumarate

Intervention Type: DRUG

Will be administered as one 300-mg tablet orally daily

Interventions

Emtricitabine

Will be administered as one 200-mg capsule orally daily

Intervention Type: DRUG

Enfuvirtide

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

Intervention Type: DRUG

Ritonavir

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

Intervention Type: DRUG

Saquinavir

Will be administered as five hard gel capsules orally twice daily

Intervention Type: DRUG

Tenofovir disoproxil fumarate

Will be administered as one 300-mg tablet orally daily

Intervention Type: DRUG

Other Intervention Names

FTC; Emtriva; ENF; Fuzeon; T-20; RTV; Norvir; Invirase; Saquinavir mesylate; TDF; Viread

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph J. Eron, Jr., MD

Role: STUDY_CHAIR

University of North Carolina, Chapel Hill

Locations

University of Colorado Hospital CRS

Aurora, Colorado, United States

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Washington U CRS

St Louis, Missouri, United States

NY Univ. HIV/AIDS CRS

New York, New York, United States

Unc Aids Crs

Chapel Hill, North Carolina, United States

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Puerto Rico-AIDS CRS

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

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.

Reference Type: BACKGROUND

PMID: 11818490 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9144290 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10837072 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9809555 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20001856 (View on PubMed)

Other Identifiers

10006

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5173

Identifier Type: -

Identifier Source: secondary_id

A5173

Identifier Type: -

Identifier Source: org_study_id