OUTLINE OF AVEG PROTOCOL 101/ACTG PROTOCOL 205

Subjects: Healthy, adult volunteers seropositive for HIV-1 infection as determined by Western Blot, with at least two initial CD4 counts with a mean of 600/mm³, no single count <450/mm³.

Schema:

Product Description: Vaccinia-derived HIV-1 IIIB rgp160 in alum and deoxycholate [IMMUNO-AG]

Time Period: First volunteer entered on 06/23/92 and last enrolled on 02/22/93; initial follow-up of 12 months per volunteer. In July 1994, follow-up was extended for an additional two years.

Clinical Sites: Johns Hopkins University AVEU/ACTG, Saint Louis University AVEU/Washington University ACTG, Vanderbilt University AVEU

Study Chair: David Schwartz, Johns Hopkins University

INCLUSION CRITERIA

• Age: >18 and <60
• Sex: Male or Female

  NOTE: For females, negative pregnancy test at time of entry and assurance that adequate birth control measures are employed for the duration of the study.

• Normal history and physical examination (generalized lymphadenopathy is acceptable)
• Normal complete blood count and lymphocytes defined as:
  • Hematocrit >33% for women; >39% for men
  • White count >3000 cells/mm³ with normal differential
  • Total lymphocyte count >800 cells/mm³
  • Platelets >100,000/mm³
  • Mean T4 cells >600 cells/mm³ for all visits (minimum of two) within 60 days prior to enrollment, with the initial screening T4 cell count >550 and no single T4 cell count <450/mm³

  NOTE: Since the volunteers are HIV seropositive, the CD4 cell count will be an important indicator of the acceleration of viral replication and CD4 cell destruction. Therefore, due to diurnal variability of CD4 counts, it is advisable to perform this test in the morning when it is most likely to be at its lowest. This will avoid large fluctuations in number from visit to visit and allow comparisons from subject to subject.

• Normal urinalysis
• Positive Western Blot test for HIV [for confirmation of HIV infection only]
• Availability for one-year follow-up
• ALT <3 x institutional upper normal limit
• Negative PPD test or normal chest X-ray with positive PPD (induration >5 mm)

  NOTE: A PPD induration of 5mm or more in an HIV positive subject is considered positive and it is the standard of care to offer Isoniazid (INH) prophylaxis for one year. It is recommended therefore that subjects who have not been previously treated be started on Isonazid as soon as possible. For individuals 35 years of age or older, a repeat ALT should be done at least 1 month after this drug has begun and prior to Day 0. Subjects with an ALT greater than three times the institutional upper limit of normal will NOT meet the inclusion criteria.

   

EXCLUSION CRITERIA

• Hepatitis B surface antigen positive
• Use of illicit drugs or significant amounts of alcohol which could potentially interfere with compliance with the study.
• Use of any potential immunomodulating agents (e.g., isoprinosine, imunothiol, lithium) within 90 days of screening.
• Use of immunosuppressive medications within the 3 months prior to enrollment.
• Vaccination against other pathogens within 4 weeks of first screening laboratory work.
• Evidence of psychiatric disorder during the year prior to enrollment that would impair adherence to the protocol.
• Evidence or history of an AIDS- or ARC-defining opportunistic infection.
• Previous use of Zidovudine (AZT) or any antiviral agent (including interferon) in the preceding 6 months.
• Evidence or history of disseminated tuberculosis, severe or persistent candidasis, oral hairy leukopenia, prolonged or very severe diarrhea, herpes zoster, or herpes simplex persisting more than 1 month.
• Active syphilis

STUDY GOALS

• To determine the safety and immunogenicity of vaccinia-derived HIV-1 recombinant envelope glycoprotein (gp160) in asymptomatic HIV infected adult volunteers.
• To compare safety and immunogenicity of two different schedules of gp160 administration.
• To examine the effects of gp160 and Hepatitis B vaccine (Engerix^®) on various markers of viral load and on selected immune parameters.