Controlling Acute or Early HIV Infection With Antiretroviral Drugs, With or Without a Candidate Vaccine

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.

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