Safety of and Immune Response to a DNA HIV Vaccine (VRC-HIVDNA009-00-VP) in HIV Infected Individuals With Acute HIV Infection

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00125099
First received: July 27, 2005
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to evaluate whether the HIV vaccine VRC-HIVDNA009-00-VP will be safe in individuals who started antiretroviral therapy during acute HIV-1 infection. The study will also test whether the vaccine can increase the immune system function in these participants.


Condition Intervention Phase
HIV Infections
Biological: VRC-HIVDNA009-00-VP
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Safety and Immunogenicity of the HIV-1 DNA Vaccine VRC-HIVDNA009-00-VP (GAG-POL-NEF-MULTICLADE ENV) in HIV-1 Infected Subjects Treated During Acute HIV Infection

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Grade 3 or 4 sign/symptom, laboratory abnormality, or death that may be related to the vaccine
  • 2 consecutive viral loads of 400 copies/ml or more while receiving HAART
  • 2 consecutive absolute CD4 cell counts of 250 cells/mm3 or more while receiving HAART
  • 2 consecutive CD4 cell counts more than 50% below the baseline CD4 cell count

Secondary Outcome Measures:
  • Tolerability (receipt of the full schedule of 4 vaccines)
  • viral load setpoint: average of the log10 viral load measures at Weeks 18, 20, and 22 after HAART withdrawl (study Weeks 48, 50, and 52)
  • Positive vaccine-elicited ELISPOT response as defined by a twofold increase from baseline that is also 100 or more spots/1,000,000 PBMCs
  • Positive vaccine-elicited intracellular cytokine staining response as defined by a twofold increase from baseline AND 300 or more spots/1,000,000 PBMCs

Enrollment: 21
Study Completion Date: September 2007
Detailed Description:

Highly active antiretroviral therapy (HAART) has greatly improved mortality and morbidity rates associated with HIV and AIDS. However, many HIV-1 infected individuals are unable to access HAART. It is therefore important to develop a safe and effective therapeutic vaccine to improve immune control of viral replication and reduce the need for antiretroviral medication. This study will evaluate the safety and immunogenicity of the HIV-1 DNA vaccine VRC-HIVDNA009-00-VP in treating HIV-1 infected individuals who initiated antiretroviral therapy during acute infection. This study will involve a supervised treatment interruption (STI) in order to determine whether therapeutic vaccination results in improved immune control of viral replication.

Participants in this study will be randomly assigned to receive either the therapeutic vaccine or placebo in addition to their regular HAART regimens. During the first part of the study, participants will receive 4 vaccinations at Weeks 0, 4, 8 and 24. All individuals completing the therapeutic vaccination phase (defined as completing at least 3 immunizations, including the Week 24 immunization) will be given the opportunity to participate in the second part of the study and undergo a supervised discontinuation of HAART. At Week 30, these participants will discontinue all antiretroviral treatment and will be closely monitored. Participants will restart HAART if they experience a significant decline in their CD4 count, an increase in their viral loads, or if their physicians recommend they resume HAART. At Week 52, all other participants can restart HAART at the discretion of their primary physician.

21 study visits will occur over a period of 52 weeks. After Week 52, monthly study visits will occur through Week 72. Study visits will last approximately two hours and will include physical exams and blood and urine collection.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Treated acute HIV-1 infection (initiated HAART during the acute retroviral syndrome AND were diagnosed by a positive HIV-1 viral load and a negative or indeterminate Western blot)
  • Minimum of 6 months of HAART, defined as 2 or more antiretroviral drugs in combination
  • At least three CD4 cell counts over 350 cells/mm3 for a period of 6 months prior to study entry
  • Screening CD4 cell count over 350 cells/mm3 within 30 days prior to study entry
  • HIV-1 RNA levels over 50 copies/ml for a period of 6 months prior to study entry
  • Screening HIV-1 RNA level less than 50 copies/ml within 30 days prior to study entry
  • Agrees to use acceptable methods of contraception

Exclusion Criteria:

  • History of serious adverse reactions to vaccines
  • History of CD4 cell count less than 250 cells/mm3, opportunistic infections, or AIDS-defining illnesses. Patients who have had one CD4 count less than 250 cells/mm3 or who have had CD4 counts less than 250 cells/mm3 for not more than 2 weeks during acute infection are not excluded.
  • History of autoimmune disease, immunodeficiency, asthma, diabetes requiring insulin or oral hypoglycemics, thyroid disease, bleeding disorder, active malignancy, viral hepatitis, or asplenia
  • Positive HBV, HCV, or syphilis test
  • Suspected allergy or adverse reaction to any component of the study agent
  • Changes in antiretroviral regimen within 6 months prior to entry due to virologic failure (not including toxicities)
  • Previous participation in STIs
  • Pregnancy or breast-feeding
  • Live attenuated vaccines or investigational research agents within the 30 days prior to study entry
  • Blood products within the 120 days prior to study entry
  • Immunoglobulin within the 60 days prior to study entry
  • Subunit or killed vaccines or allergy treatments with antigen injections within the 14 days prior to study entry
  • Prior experimental HIV vaccines
  • Certain immunosuppressive medications within the 6 months prior to study entry
  • Current TB prophylaxis or therapy
  • Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
  • Serious illness requiring systemic treatment and/or hospitalization. An individual who has either completed therapy OR is clinically stable for at least 14 days prior to study entry is eligible.
  • Anti-dsDNA antibody greater than the upper limit of normal
  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: NCT00125099

Locations
United States, California
Ucsd, Avrc Crs
San Diego, California, United States, 92103
United States, Massachusetts
Brigham and Women's Hosp. ACTG CRS
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
United States, New York
Aaron Diamond AIDS Research Ctr. AIEDRP
New York, New York, United States, 10021
United States, Washington
UW Primary Infection Clinic CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Dan H. Barouch, MD, PhD Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis
Study Chair: Eric S. Rosenberg, MD Massachusetts General Hospital, Division of Infectious Diseases
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00125099     History of Changes
Other Study ID Numbers: A5187, 10010, ACTG A5187
Study First Received: July 27, 2005
Last Updated: May 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Acute Infection
Treatment Experienced
Treatment Interruption
HIV Therapeutic Vaccine

Additional relevant MeSH terms:
Infection
Communicable Diseases
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 September 22, 2014