Vaccine Therapy, Incomplete Freund's Adjuvant, and GM-CSF in Treating Patients With HIV

OBJECTIVES:

Primary

• Assess the safety of vaccination comprising E1M184V peptide with incomplete Freund's adjuvant in combination with sargramostim (GM-CSF) in patients with HIV who are HLA-A2 positive.
• Assess, preliminarily, the ability of E1M184V peptide vaccine to induce a cytotoxic T-cell response, defined by ELISPOT assay, in these patients.

Secondary

• Explore, preliminarily, the effect of this regimen on HIV viral load and CD4 count in these patients.
• Explore, preliminarily, the development of lamivudine or emtricitabine resistance in patients who subsequently receive lamivudine or emtricitabine.
• Explore, preliminarily, the ability of E1M184V peptide vaccine to induce a cytotoxic T-cell response as assessed by HLA-A2 class I tetramers and intracellular interferon gamma production after stimulation with E1M184V.

OUTLINE: This is a pilot study.

Patients receive vaccination comprising E1M184V peptide and incomplete Freund's adjuvant subcutaneously (SC) on day 1 in weeks 0, 4, 8, 12, and 16. Patients also receive sargramostim (GM-CSF) SC immediately after vaccination and once daily on days 1-4. Some patients do not receive GM-CSF after the first 2 doses of vaccine. Treatment continues in the absence of unacceptable toxicity.

Patients undergo blood collection at baseline and at 4, 12, 20, 36, and 52 weeks for biomarker/laboratory analysis. Assays may include immunoenzyme techniques and viral genotyping.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• HIV-1 infection confirmed by Western blot and enzyme-linked immunosorbent assay
• HLA-A2 positive by polymerase chain reaction-sequence specific primers
• CD4 T-cell count ≥ 300/mm³
• Must be receiving stable regimen of highly active antiretroviral therapy (HAART) that does not include lamivudine or emtricitabine for ≥ 1 month prior to study entry

• Patients on HAART, including lamivudine or emtricitabine, for which there is a medically appropriate regimen that does not include lamivudine or emtricitabine, are eligible if willing to change antiretrovirals
• Viral load < 50 copies/mL for 1 month prior to study entry

PATIENT CHARACTERISTICS:

• See Disease Characteristics
• ECOG performance status 0-1
• Life expectancy ≥ 6 months
• Hemoglobin ≥ 9 g/dL
• WBC ≥ 1,000/mm³
• Absolute neutrophil count ≥ 750/mm³
• Platelet count ≥ 75,000/mm³
• PT and PTT ≤ 120% of control unless lupus anticoagulant detected
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 7.5 mg/dL with direct fraction ≤ 0.7 mg/dL if on protease inhibitor therapy or due to Gilbert's syndrome)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No hepatitis B surface antigen (HBsAg) or a prior history of HBsAg while on lamivudine or emtricitabine

• Prior treatment with tenofovir and currently HBsAg negative allowed
• No evidence of a severe or life-threatening infection other than HIV within the past 6 months
• No opportunistic infections requiring systemic therapy within the past month
• No active malignancy, except for basal cell carcinoma
• No known hypersensitivity to incomplete Freund's adjuvant or incomplete Freund's adjuvant VG (vegetable-grade), E1M184V peptide, or sargramostim (GM-CSF)
• No other abnormality that would be scored as ≥ grade 3 toxicity, except any of the following (if asymptomatic):

• Hyperuricemia of grade 4 (without physiologic consequences)
• Elevation of lactate dehydrogenase ≥ grade 3
• Elevation of creatine phosphokinase (CPK) ≥ grade 3
• Hypophosphatemia ≥ grade 3 (if patient is on tenofovir)
• Elevation of alkaline phosphate of grade 3
• Hyperamylasemia of ≥ grade 3 allowed if any of the following criteria are met:

• Macroamylasemia
• Lipase ≤ 2 times ULN
• Lymphopenia grade 3
• No other condition that, in the opinion of the investigator, would preclude compliance with study requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No systemic corticosteroids within the past 3 weeks

• Concurrent systemic corticosteroids allowed in the short term only
• Physiologic replacement doses of steroids allowed
• No prior vaccination with a vaccine that includes all or part of the reverse transcriptase of HIV-1
• No other concurrent investigational drugs or vaccinations
• No concurrent lamivudine or emtricitabine