Controlling Acute or Early HIV Infection With Antiretroviral Drugs, Without a Candidate Vaccine.As Reported Previously, the Candidate Vaccie Was Not Provided by the Maufacturer as Promised

• ClinicalTrials.gov Identifier: NCT00238459
• Recruitment Status: Completed
• First Posted: October 13, 2005
• Last Update Posted: November 20, 2013
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Fred T. Valentine, National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

The purpose of this study is to determine the role of HIV-specific CD4 T cell responses and immune responses dependent upon these CD4 responses that develop when antiretroviral drugs are started during acute or recent HIV infection, whether these CD4 responses can be enhanced with a therapeutic HIV vaccine (HIV-1 immunogen), and what pattern of HIV-specific immune responses is associated with control of HIV upon discontinuation of antiretroviral drugs during an analytical therapeutic interruption. Participants will be treatment-naive adults with acute or early HIV infection who will choose to start or not start anti-HIV drugs at the beginning of the study. NOTE: In August 2007 we were notified by the manufacturer of the candidate vaccine that they were no longer making the vaccine, and that the vaccine would no longer be available. Unfortunately too few participants have received either the vaccine or placebo to conclude anything about efficacy. No safety problems occurred.

Condition or disease	Intervention/treatment
HIV Infections	Drug: Patients elected to take licensed drugs. The vaccine was not provided for evaluation; Drug: multiple licensed drugs not randomized; Drug: multiple licensed antiretroviral drugs; not randomized; Other: Intended vaccine not provided, Licensed drugs provided, but were not investigated

Detailed Description:

In some HIV patients with acute or early infection, effective long-term immunological control of HIV occurs, indicating that before HIV caused irreparable damage, their immune systems were able to mount an effective immune response to HIV. However, it is unknown how the immune systems of such patients with acute or early infection are able to develop and maintain effective memory CD4 immune responses. In other HIV patients, it is the destruction of CD4 cells and an ever-weakening immune system that leads to the progression of HIV disease. HIV-1 immunogen is a whole killed gp120-depleted HIV vaccine composed of an HIV-1 isolate (HZ321) from serum collected from a patient in Zaire in 1976. The vaccine contains proteins from HIV subtypes A and G. By injecting these particles into HIV infected people, the immune system may be stimulated to mount a greater immune response not only to the killed HIV particles of the vaccine but also to real virus particles and HIV infected cells in these people. Also, because HIV-1 immunogen is based on whole inactivated virus, it may stimulate broader immune responses that are capable of suppressing more diverse HIV strains than currently available vaccine preparations that are based on single subunit proteins of HIV. This study was planned to evaluate the safety and efficacy of a therapeutic HIV vaccine, HIV-1 immunogen, in conjunction with STIs, in controlling HIV infection during acute or early infection. Participants will be antiretroviral therapy (ART)-naive and will choose to either start or not start ART in this study.

Participants will elect to start or not start ART at the start of this study. Those participants who choose not to begin ART will not receive any intervention during this study but will be followed for the entire length of the study. Those participants that choose to begin ART will start taking study-approved ART in Step 1 of the study. Only patients who have a viral load of less than 50 copies/ml by Week 24 will proceed to Step 2; all other patients who begin ART will continue on study-approved ART but will not receive any vaccinations over the course of the study. Step 2 is the STI part of the study. In Step 2, patients will stop ART and will be randomly assigned to receive therapeutic vaccine or placebo injections at three timepoints: at the start of Step 2 and 12 and 24 weeks after starting Step 2. Injections will be given only to patients who have been on ART for at least 48 weeks; patients will receive their assigned injections 36 weeks after their first viral load reading of less than 50 copies/ml. A patient will enter Step 3 after having restarted ART for a minimum of 8 weeks after Step 2 ends, when the patient's viral load is less than 400 copies/ml and CD4 count is greater than 250 cells/ml. Entry into Step 4, which will include additional retreatment and revaccination, may be necessary for some participants, depending on individual immune response to the study-given ART and the injections.

The ART participants in this study will receive either study-provided ART or another approved ART; however, only study-provided ART will be provided by the study. Viral load and CD4 count will be closely monitored and will guide retreatment and revaccination as necessary. Blood collection will occur at all visits. A physical exam will occur at most visits. Urine collection and quality of life and adherence questionnaires will occur at selected visits.

NOTE: In August 2007 we were notified by the manufacturer of the candidate vaccine that they were no longer making the vaccine, and that the vaccine would no longer be available. Unfortunately too few participants have received either the vaccine or placebo to conclude anything about efficacy. No safety problems occurred.

Study Design

• Study Type: Observational
• Actual Enrollment: 58 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Immunopathogenesis of Acute and Early HIV Infection and the Role of HIV-Specific CD4 T Cell Responses and the Effect of Their Enhancement by Potent Antiretroviral Drugs and an HIV Vaccine Adequate Vaccine Was Not Provided.
• Study Start Date: July 2005
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: October 2013

Groups and Cohorts

Group/Cohort	Intervention/treatment
Recently infected patients; Cohort 1)Patients elcted to be immediately treated with licensed drugs:21 patients Cohort 2) Or to delay treatment until clinically indicated:16 patieints	Drug: multiple licensed drugs not randomized
A vaccine,HIV-1 immunogen was not provided for evaluation; In the intial design, acandiate HIV vaccine was to be evaluated, but in August 2007 the manufacturer refused to provide vaccine to allow this study to evaluate the effect of a vaccine on control of HIV. Therefore the study became an observational study of the effects of early versus delayed initiation of antiretrovral therapy on the preservation of anti-HIV immune responses and the ability of patients to control virus after a closely monitored discontinuation of therapy.	Drug: Patients elected to take licensed drugs. The vaccine was not provided for evaluation; Note:In August 2007 we were notified by the manufacturer that the experimental vaccine was no longer being made and would no longer be available for this study. Too few participants have received the vaccine or placebo to conclude anything about potential efficacy; Drug: multiple licensed antiretroviral drugs; not randomized; Other: Intended vaccine not provided, Licensed drugs provided, but were not investigated

Outcome Measures

Primary Outcome Measures :

1. Effects of treatment on HIV-specific immune responses. [ Time Frame: Weekly and then monthly after stopping antiretroviral drugs ]

Secondary Outcome Measures :

1. Immune control of HIV after stopping antiretroviral drugs. [ Time Frame: Weekly and then monthly after stopping antirretroviral drugs ]

Biospecimen Retention:   Samples Without DNA

Sequential samples from patients with acute and recent HIV infection

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Acutely HIV infected patients: virus positive antibody negative Recently HIV infected patients: virus positive, low titers of antibody

Criteria

Inclusion Criteria:

• Acute or early HIV infection
• ART naive
• Willing to use acceptable forms of contraception

Exclusion Criteria:

• Allergy/sensitivity to any components of the vaccine
• Currently involuntarily incarcerated
• Pregnant or breastfeeding

Contacts and Locations

Locations

United States, New York

New York University School of Medicine

New York, New York, United States, 10016

Canada, Quebec

McGill University and University of Montreal

Montreal, Quebec, Canada

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Fred Valentine, MD; NYU Langone Health

More Information

Additional Information:

Click here for more information about the Center of AIDS Research at the New York University School of Medicine 

Publications:

Peters BS. The basis for HIV immunotherapeutic vaccines. Vaccine. 2001 Dec 12;20(5-6):688-705. doi: 10.1016/s0264-410x(01)00394-2.

Stekler J, Collier AC. Primary HIV Infection. Curr HIV/AIDS Rep. 2004 Jun;1(2):68-73. doi: 10.1007/s11904-004-0010-2.

Wahren B, Liu M. Therapeutic vaccination against HIV. Expert Rev Vaccines. 2004 Aug;3(4 Suppl):S179-88. doi: 10.1586/14760584.3.4.s179.

• Responsible Party: Fred T. Valentine, Professor of Medicine, National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00238459
• Other Study ID Numbers: 5P01AI57127-2; 5P01AI057127 ( U.S. NIH Grant/Contract )
• First Posted: October 13, 2005
• Last Update Posted: November 20, 2013
• Last Verified: November 2013

Keywords provided by Fred T. Valentine, National Institute of Allergy and Infectious Diseases (NIAID):

Immunity to HIV; Acute Infection; Treatment Naive; Treatment Interruption; Structured Treatment Interruption; STI

Additional relevant MeSH terms:

Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Disease Attributes; Pathologic Processes; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Anti-Retroviral Agents; Vaccines; Immunologic Factors; Physiological Effects of Drugs; Antiviral Agents; Anti-Infective Agents