Phase I Protocol for the Evaluation of the Safety and Immunogenicity of Vaccination With Synthetic HIV Envelope Peptides in Patients With Early Human Immunodeficiency Virus Infection
Phase I Protocol for the Evaluation of the Safety and Immunogenicity of Vaccination With Synthetic HIV Envelope Peptides in Patients With Early Human Immunodeficiency Virus Infection
Synthetic HIV Peptide Vaccines (Treatment Protocol)

 We are conducting a study to evaluate the safety of two peptide vaccines (given alone or in
 combination) in patients with early HIV infection. Patients entered onto the study must have
 >500 CD4 cells/mm(3) and have preserved cardiac, hepatic, renal, and bone marrow function.
 Patients must be off all anti-retroviral therapy for at least 6 months and may not have
 received any experimental HIV vaccines. The vaccines being testing in this trial are
 comprised of short peptide segments of the HIV envelope, including the V3 loop. In animal
 studies, the peptides were able to induce neutralizing antibodies as well as cytotoxic T
 responses to HIV. This will be the first trial in which they are given to humans. The study
 will last for approximately one year, during which time the volunteers will receive 6 peptide
 vaccines under the skin. For more information, please call Tino Merced-Galindez, R.N. at
 (301) 496-8959 or Dr. Richard Little at (800) 772-5464.
Assessment of toxicity and immunogenicity of two HIV-1 derived peptide vaccines in Montanide
 ISA-51 (incomplete Freund's adjuvant) given singly and in combination.
Patients who are seropositive, documented by a licensed ELISA with a confirmatory Western
 blot assay for HIV with greater than or equal to 500 CD4+ cells/mm(3) at the time of
 screening who also meet either of the 2 following criteria:

 During acute infection there is no lower limit for the CD4 count (acute infection is
 defined for this protocol as the 6 month period after diagnosis of HIV seropositivity in a
 patient with documented negative HIV serology within the 6 months prior to diagnosis of HIV
 seropositivity) OR;

 If there is a history of CD4 count less than 300 cells/mm(s) at any point after initial HIV
 seropositive diagnosis patient will not be eligible, unless this count was during the time
 of acute infection.

 Ambulatory status, and ability and willingness to give informed consent.

 Must be over 18 years old and have an estimated life expectancy of more than 12 months.

 Hgb greater than or equal to 12 g/dl for men and 11 gm/dl for women.

 ANC greater than or equal to 1000/mm(3).

 Creatinine greater than or equal to 1.5 mg/dl or creatinine clearance greater than 50
 ml/min.

 LFT: AST and ALT less than or equal to 3x upper limit of normal IU/ml for enrollment.
 Alkaline phosphatase less than or equal to 2.5x ULN.

 Bilirubin within normal limits, except for known Gilbert's Syndrome or if patient is on
 protease inhibitor therapy. For patients on protease inhibitor therapy, direct bilirubin
 less than or equal to 0.3 mg/dl and indirect bilirubin less than or equal to 4.5 mg/dl.

 Patients must be willing to comply with a medical regimen of highly active antiretroviral
 therapy, and must be on a stable antiretroviral regimen for a minimum of 4 weeks prior to
 the first vaccination.

 Patients should not be receiving antiretroviral therapy or should not have received
 antiretroviral therapy within 6 months.

 Patients without actual or suspected allergies to any component of vaccine.

 No prior vaccines for HIV.

 Patients should not have received treatment with the following meds at study entry or
 within preceding 3 months - agents with immunomodulating activity, parenteral therapies,
 HIV drugs, vaccines, interferons, corticosteroids, any growth factors.

 No prior Aids defining OI.

 No active life threatening infection.

 No severe malabsorption.

 No evidence of Kaposi Sarcoma or other tumor - likely to require cytotoxic antitumor
 therapy within 6 months of entering study. Must complete acute therapy for infections at
 least 14 days prior to entry.

 No pregnancy. Female patients of child bearing potential must have a negative pregnancy
 test prior to vaccine administration. Males and females must agree to use effective birth
 control methods during the course of vaccination.

 No patients in whom there is a medical contraindication or potential problems in complying
 with the requirements of the protocol.