Vaccine (ALVAC-HIV vCP1452) Use and Intermittent Withdrawal of Anti-HIV Drugs in Patients With HIV

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00011011
First received: February 8, 2001
Last updated: July 30, 2013
Last verified: July 2013
  Purpose

Long-term control of HIV depends on improvement in an individual's immune system. The purpose of this study is to see if either stopping anti-HIV drugs for short periods of time and/or adding a vaccine to the anti-HIV drugs being taken will help to better control HIV infection. The study will test whether these treatment approaches are safe. The HIV vaccine in this study has been tested in people who did not have HIV infection and improved the way their immune system worked. This study will evaluate whether these same immune system changes happen in people with HIV, and, if such changes do occur, assess whether these changes help to improve control of HIV in these patients.


Condition Intervention Phase
HIV Infections
Biological: ALVAC(2)120(B,MN)GNP (vCP1452)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized Phase I/II Pilot Study of Intermittent Withdrawal of Antiretroviral Therapy as an Immunization Strategy and Double-Blinded Immunization With ALVAC-HIV vCP1452 in Subjects With Persistent CD4+ Cell Counts Greater Than 400 Cells/mm3 and Plasma HIV-1 RNA Levels Less Than 50 Copies/ml

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Enrollment: 94
Study Start Date: February 2001
Study Completion Date: October 2006
Detailed Description:

The best hope for long-term control of HIV infection in an individual likely rests with the resumption of effective HIV-specific immune responses. Intermittent antiretroviral therapy (ART) withdrawal, as an attempt to "immunize" the subject with his/her own active viral quasi-species population, represents an alternative approach to traditional immunization strategies. This study hopes to determine whether intermittent ART withdrawal serves to stimulate HIV-specific immune responses and control of viral replication. This approach will be compared with vaccination with ALVAC-HIV vCP1452. In addition, it is conceivable that intermittent ART withdrawal could boost and broaden the prime response to exogenous vaccine; that will also be studied.

Patients will continue receiving their potent ART (not provided by the study) and will be randomly assigned to one of four treatment strategies as follows:

Arm A: ALVAC placebo and potent ART for 92 weeks with a single 12- to 20-week therapy withdrawal period; Arm B: ALVAC placebo and potent ART for 84 weeks with a 4- to 6-week therapy withdrawal period, a 4-week therapy withdrawal period, and a 12- to 20-week therapy withdrawal period; Arm C: ALVAC vCP1452 vaccine and potent ART for 92 weeks with a single 12- to 20-week therapy withdrawal period; and Arm D: ALVAC vCP1452 vaccine and potent ART for 84 weeks with a 4- to 6-week therapy withdrawal period, a 4-week therapy withdrawal period, and a 12- to 20-week therapy withdrawal period.

Immunizations of placebo or vaccine wil be administered in 3 separate sets of 3 injections per set (9 total) and immunization schedules are the same for all patients, those undergoing intermittent therapy withdrawal (Arms B and D) and those who are not (Arms A and C).

This is a multiple-step study. Patients in Arms B and D will receive a 4-week period of potent ART therapy along with the first set of immunizations (Step 1) followed by therapy withdrawal for 4 to 6 weeks (Step 2). Alternating periods of therapy resumption (Step 3, consisting of 16 weeks on potent ART with the second set of vaccine administrations), a second therapy withdrawal (Step 4 for 4 weeks), and another therapy resumption (Step 5, consisting of 16 weeks on potent ART with the third set of vaccine administrations) will follow. Patients in Arms A and C will remain on Step 1 for the first 44 weeks on study.

After 44 to 46 weeks on study, patients in all arms will have therapy withdrawn for 12 to 20 weeks (Step 6). Following completion of Step 6, patients whose viral load are below 10,000 copies/ml will be encouraged to remain off potent ART (Step 7) until completion of the study, as long as CD4 T-cell levels remain 50 percent or more of their baseline levels. Participants who successfully complete Step 7 will be invited to enter Step 9, a 48-week optional protocol extension. Otherwise, patients will restart their potent ART regimens (Step 8) and receive virologic and CD4 T-cell monitoring until completion of the study.

All patients will be monitored at regular clinic visits. Viral load and CD4 T-cell counts will be measured at each visit. Patients in all arms may participate in substudy A5101s (Male Genital Secretions) or substudy A5137s (Female Genital Secretions), and patients in Arms B and D may participate in substudy A5111s (Latent Infected T-Cell Clearance).

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Step 1

  • HIV infection
  • CD4 count greater than 400 cells/mm3 within 6 months before study entry
  • Current, persistent viral load below 400 copies/ml for 6 months before study entry and under 50 copies/ml at study screening
  • Currently receiving their first combination ART regimen (3 or more antiretrovirals) for at least 4 weeks before screening, or if the current potent ART regimen is not their first potent ART regimen, must have been receiving the current regimen for at least 4 weeks prior to screening
  • Negative pregnancy test within 45 days before study entry
  • Acceptable methods of contraception
  • Provide informed consent

Exclusion Criteria

  • Immunomodulators within 45 days of study entry such as systemic corticosteroids, interferons, interleukins, thalidomide, sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]), dinitrochlorobenzene (DNCB), thymosin alpha, thymopentin, inosiplex, polyribonucleoside, and ditiocarb sodium
  • Abacavir within 8 weeks of study entry
  • Infection or medical illness within 14 days of study entry
  • Cancer that may require systemic therapy
  • History of lymph node radiation therapy
  • Prior HIV vaccine
  • Received hydroxyurea within 45 days of study entry
  • Close contact with canaries through work (e.g., breeding farms, bird shops); patients with a pet canary are not excluded
  • Abuse or dependence on drugs or alcohol
  • Allergic to albumin
  • Pregnant or breastfeeding
  • Infected with HIV within 1 year of study entry
  • Interruption of potent ART for more than 7 consecutive days within 1 year of study entry
  • History of allergy to egg proteins or neomycin
  • History of other serious acute allergic reactions (e.g., anaphylaxis, allergy-induced asthma, Stevens-Johnson syndrome, toxic epidermal necrolysis)
  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 ClinicalTrials.gov identifier: NCT00011011

Locations
United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90095
Ucsf Aids Crs
San Francisco, California, United States, 94110
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States, 63110
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
AIDS Care CRS
Rochester, New York, United States, 14607
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, United States, 02906
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Jeffrey M. Jacobson, MD Beth Israel Medical Center
Study Chair: Ian Frank, MD Division of Infectious Diseases, University of Pennsylvania
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00011011     History of Changes
Other Study ID Numbers: A5068, 10072, Substudy AACTG A5101s, Substudy AACTG A5111s, Substudy AACTG A5137s, ACTG A5068, AACTG A5068
Study First Received: February 8, 2001
Last Updated: July 30, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Drug Administration Schedule
AIDS Vaccines
CD4 Lymphocyte Count
RNA, Viral
Anti-HIV Agents
Viral Load
HIV Therapeutic Vaccine
Treatment Interruption

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on July 28, 2014