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
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Observational

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.
    

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.
    

Intervention name(s): Patients elected to take licensed drugs. The vaccine was not provided for evaluation; multiple licensed drugs not randomized; multiple licensed antiretroviral drugs; not randomized; Intended vaccine not provided, Licensed drugs provided, but were not investigated
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): 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
Intervention MeSH terms: Anti-Retroviral Agents; Vaccines
Observational model: Case-Control
Time perspective: Prospective
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
      
Biospecimen description: 
      Sequential samples from patients with acute and recent HIV infection
    
Keywords: Immunity to HIV; Acute Infection; Treatment Naive; Treatment Interruption; Structured Treatment Interruption; STI