A Study to Evaluate of the Efficacy of Enfuvirtide During the Induction Phase of Therapy

Viral Decay Kinetics During Induction Therapy With or Without the Use of Enfuvirtide in HAART-naÃ-ve Patients With Advanced HIV

We hypothesize that using a potent antiretroviral such as Enfuvirtide during the induction phase of HAART therapy will lead to faster clearance of virus and infected cells, and lower number of minority variant HIV-1 strains.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Efavirenz, lamivudine, and tenofovir; Drug: Enfuvirtide

Detailed Description

This is an 48 week Phase 4, open label, randomized, prospective, pilot proof of concept study to evaluate the use of Enfuvirtide in an induction/maintenance treatment model. Patients meeting inclusion criteria will be stratified into two groups according to HIV-1 RNA viral loads (less than 300,000 copies/ml and greater than 300,000 copies/ml). Thereafter, patients will be block randomized (the size of each block will be two patients) into one of two treatment arms.

All patients will receive Efavirenz 600mg once a day, Lamivudine 300 mg once a day, and Tenofovir 300mg once a day. After randomization, one half of the patients will receive no additional treatment, while the other half will receive Enfuvirtide 90mg sq BID until the viral load is <50 x 2 consecutive visits or 12 weeks (whichever comes first).

• Study Type: Interventional
• Enrollment (Anticipated): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Institute of Human Virology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age: 18 to 70 years of age.
2. Sex: Male or Female.
3. Documented HIV-1 seropositive by Western Blot, Elisa, or HIV-1 viral load.
4. Naïve to HAART.
5. Viral load >100,000c/ml.
6. CD4<200c/ml.
7. Volunteers must be willing and able to provide written informed consent to participate in the study.
8. Available for at least 48 weeks of follow-up.

Exclusion Criteria:

1. Volunteers with an acute and clinically significant medical event as determined by the investigator to result in a life expectancy less then 12 months despite ART.
2. Volunteers with current psychiatric illness, alcohol abuse or illicit drug use that in the opinion of the Principal Investigator may interfere with patient's ability to comply with protocol requirements.
3. Renal insufficiency (Estimated Creatinine clearance of <60ml/min.)
4. Patients with malabsorption or severe chronic diarrhea for more than 30 days.
5. Inability to consume adequate oral intake (defined as inability to eat at least 1 meal per day).
6. Current treatment for malignancy other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
7. Any other medical condition which, in the opinion of the investigator, might interfere with completion of the study or evaluation of the results.
8. Pregnancy or breastfeeding
9. In a female capable of child bearing, unwillingness to use effective barrier contraception or abstinence
10. Patient who is currently receiving an experimental medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Treatment; Efavirenz 600mg once daily, Lamivudine 300mg once daily and Tenofovir 300mg once daily	Drug: Efavirenz, lamivudine, and tenofovir; Efavirenz -600mg once daily, lamivudine- 300mg once daily, and tenofovir 300mg once daily; Other Names: Atripla, Epivir and Viread
Experimental: Standard Treatment Plus Enfuvirtide; Efavirenz 600mg once daily, Lamivudine 300mg once daily, Tenofovir 300mg once daily and enfuvirtide 90mg subcutaneously twice a day until the viral load is less than 50copies for 2 consecutive visits or 12 weeks (whichever comes first).	Drug: Efavirenz, lamivudine, and tenofovir; Efavirenz -600mg once daily, lamivudine- 300mg once daily, and tenofovir 300mg once daily; Other Names: Atripla, Epivir and Viread; Drug: Enfuvirtide; subcutaneously twice a day; Other Names: Fuzeon (T-20)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to viral suppression below 50c/ml.	The study is 48 weeks long and the time to viraL suppression will vary depending on the subject. Or there is the possibility that they do not supress	Individual

Secondary Outcome Measures

Outcome Measure	Time Frame
Log viral copy/ml decrease over time during phase 1 and phase 2.	Over the 48 week study period
Development of clinical mutations.	Over the 48 week study period
Development of sub-clinical mutations (minority variants)	Over the 48 week study period
Viral suppression (below 50c/ml) at 24 and 48 weeks.	At 24 and 48 weeks
Time to loss of viral response. Loss of viral response defined as:	Over the 48 week study period
Less then 2.0 log decrease in viral load at week 8.	Week 8
Inability to achieve Viral load <50c/ml by week 12.	Week 12
Viral load >50c/ml on 2 consecutive measurements taken 2 weeks apart after viral	Over the 48 week study period
suppression <50c/ml has occurred	Over the 48 week study period
Rate and quantity of HIV-1 proviral DNA decay.	Over the 48 week study period
Safety and tolerability.	Over the 48 week study period

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Ronald B Reisler, MD, MPH, University of Maryland, School of Medicine, Department of Infectious Disease

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: June 23, 2006
• First Submitted That Met QC Criteria: June 23, 2006
• First Posted (Estimate): June 27, 2006

Study Record Updates

• Last Update Posted (Actual): May 11, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Lamivudine; Enfuvirtide; Efavirenz
• Other Study ID Numbers: H-26280