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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00011011

Collaborator

(none)

Enrollment

Locations

67.9

Duration (Months)

5.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: ALVAC(2)120(B,MN)GNP (vCP1452)	Phase 1/Phase 2

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

94 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double

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

Study Start Date :

Feb 1, 2001

Actual Study Completion Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35294
2	UCLA CARE Center CRS	Los Angeles	California	United States	90095
3	Ucsf Aids Crs	San Francisco	California	United States	94110
4	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
5	Washington U CRS	Saint Louis	Missouri	United States	63110
6	Beth Israel Med. Ctr., ACTU	New York	New York	United States	10003
7	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
8	AIDS Care CRS	Rochester	New York	United States	14607
9	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
10	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
11	Case CRS	Cleveland	Ohio	United States	44106
12	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
13	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
14	Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.	Philadelphia	Pennsylvania	United States	19104
15	The Miriam Hosp. ACTG CRS	Providence	Rhode Island	United States	02906
16	University of Washington AIDS CRS	Seattle	Washington	United States	98104

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: Jeffrey M. Jacobson, MD, Beth Israel Medical Center
Study Chair: Ian Frank, MD, Division of Infectious Diseases, University of Pennsylvania