OUTLINE OF PROTOCOL 103A

Subjects: Adult volunteers with HIV-1 infection and CD4 counts >600/mm³ and who do not have plasma viremia.

Schema:

Product Description: Yeast-derived HIV-1 SF-2 rgp120 (ENV 2-3) in combination with MF59 adjuvant emulsion ± MTP-PE (muramyl tripeptide-phosphatidylethanolamine) adjuvant [Chiron/BIOCINE]

Time Period: First volunteer entered on 03/23/92 and last enrolled on 09/28/92; follow-up of 6 months after the last injection.

Clinical Sites: University of Rochester and University of Washington

Study Chair: Lawrence Corey, University of Washington

INCLUSION CRITERIA

• Age: 18-50
• 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 physical examination (generalized lymphadenopathy, seborrheic dermatitis are acceptable)
• Normal complete blood count and lymphocytes defined as:
  • Hematocrit >32% for women; >34% for men
  • White count >3000 cells/mm³ with normal differential
  • Total lymphocyte count >800 cells/mm³
  • Average CD4 cell count >600/mm³ on two or more occasions in the 6 weeks prior to enrollment, with no single count <550/mm³ [2/92] *
  • Platelets >75,000/mm³
• Normal urinalysis
• ALT <3 x institutional upper normal limit
• Positive ELISA and Western Blot test for HIV
• Availability for 10 months of follow-up post vaccination
• Negative HIV plasma culture in the 4 months prior to enrollment

EXCLUSION CRITERIA

• Use of any other investigational agent within 30 days.
• Use of illicit drugs or significant amounts of alcohol that in the opinion of the Principal Investigator, would interfere with compliance with the study.
• Use of zidovudine (AZT) for more than 30 days in the preceding 6 months, or any zidovudine within the last 30 days; use of any non-AZT antiretroviral drug.
• Use of any potential immunomodulating agents (e.g., isoprinosine, imunothiol, lithium) within 90 days of screening.
• Use of immunoglobulins within 60 days.
• Use of immunosuppressive medications during the past 3 months
• Evidence of psychological disorder during the past year that would impair adherence to the protocol.
• Evidence or history of an AIDS defining opportunistic infection.

STUDY GOALS

• To determine the safety and immunogenicity of ENV 2-3 in combination with MTP-PE/MF59 in adult volunteers with HIV infection.
• Study extension: To evaluate the safety and immune response to a fourth and fifth dose of 30 µg ENV 2-3 formulated in MTP-PE/MF59 or placebo (MF59).

SPECIAL CONSIDERATIONS

If the subject meets one or both of the following criteria, his/her participation in the study will be modified:

• Absolute CD4 counts of less than 450/mm³ on two successive occasions separated by 72 hours after the first dose of vaccine. The CD4 counts at this level may vary with time of day and activity of person; and, in addition, as we are screening via CD4 counts for those with "high counts," we expect some "regression to the mean" between screening and baseline values. As such, we feel a CD4 count of <450 for two successive occasions is a modest level to initiate therapy for the subject. Such individuals will be referred to their personal physicians for possible AZT therapy. If they have received only one dose of vaccine they will be replaced. If they have received 2 doses of vaccine, they will be followed per the study protocol.
• If a subject develops AIDS or ARC symptoms, they will be referred to their health care provider for AZT therapy following approved FDA criteria and vaccination will stop, but they will be followed per study protocol.

* Criteria as modified at date indicated