A Phase I/II Double-Blind Controlled Trial to Determine the Safety and Immunogenicity of HIV-1 MN rgp160 Immuno AG Vaccine Therapy in HIV-Infected Individuals With Greater Than or Equal to 500/mm3 CD4+ T Cells and 200-400/mm3 CD4+ T Cells

Study Overview
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Brief Summary
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To evaluate the safety and immunogenicity of HIV-1 MN rgp160 (Immuno-AG) in HIV-infected patients. To evaluate the immunogenicity of HIV-1 MN rgp160 immunogen by lymphocyte proliferation, specific antibody responses, and DTH reaction. To describe the durability of the immunogen in patients who respond to the first 7 injections when they are boosted every 8 weeks for an additional 6-12 months [AS PER AMENDMENT 11/12/96: stratum 1 patients only]. To describe the ability of the immunogen to induce a response after an additional 6-12 months of injections among patients who did not respond to the first 7 injections [AS PER AMENDMENT 11/12/96: stratum 1 patients only]. HIV-specific cellular immune responses appear to play an important role in HIV disease progression since both T helper and cytotoxic function against HIV decrease with disease progression.

Detailed Description
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HIV-specific cellular immune responses appear to play an important role in HIV disease progression since both T helper and cytotoxic function against HIV decrease with disease progression. Patients with CD4 counts greater than or equal to 500 cells/mm3 are randomized to receive HIV-1 MN rgp160 (Immuno-AG) or control. Patients with CD4 counts 50-499 cells/mm3 receive didanosine (ddI) and are then randomized to receive ddI plus vaccine or control. Vaccine or control is given every 4 weeks for 7 injections, then every 8 weeks for 6-12 months or until 1 year after the last patient is randomized. AS PER AMENDMENT 11/12/96: Stratum 1 is composed of 16 subjects with CD4+ T cells greater than or equal to 500 mm3. These subjects are randomized to vaccine therapy or vaccine control. HIV-1 MN rgp160 vaccine or control is given every 4 weeks for 7 injections (Schedule 1), then every 8 weeks until 52 weeks after the last subject has been randomized to stratum 1 (Schedule 2). Stratum 1 patients receive ddI or d4T only if their CD4 cell count has a sustained decrease on 2 consecutive occasions 10-14 days apart and/or HIV/RNA plasma viral load increases to greater than 10,000 copies/ml on 2 consecutive occasions 10-14 days apart. Stratum 2 is composed of 30 subjects with CD4+ T cells 200-400/mm3; accrual to this stratum was activated based on preliminary results from stratum 1 (closed as of 4/5/97). Patients on stratum 2 (open as of 3/4/97) initially receive ritonavir at escalating doses for 2 weeks. Subjects then have ddI and d4T added to the regimen for 7 weeks. Subjects are then randomized to vaccine therapy or vaccine control every 4 weeks for 7 injections, with ritonavir/ddI/d4T continued during vaccine therapy. AS PER AMENDMENT 3/23/98: As of 6/1/98 vaccine consists of sodium chloride for injection (USP).

Official Title
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A Phase I/II Double-Blind Controlled Trial to Determine the Safety and Immunogenicity of HIV-1 MN rgp160 Immuno AG Vaccine Therapy in HIV-Infected Individuals With Greater Than or Equal to 500/mm3 CD4+ T Cells and 200-400/mm3 CD4+ T Cells

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Ritonavir
* Biological: gp160 Vaccine (Immuno-AG)
* Drug: Stavudine
* Drug: Didanosine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Concurrent Medication: Allowed: ddI [AS PER AMENDMENT 11/12/96: and d4T]. (Note: Patients in the stratum receiving only vaccine or control may take ddI [AS PER AMENDMENT 11/12/96: and d4T] ONLY IF their CD4 counts have shown a sustained decrease on two consecutive occasions 10-14 days apart.) PCP prophylaxis. Treatment for acute conditions, as indicated. AS PER AMENDMENT 11/12/96: Co-enrollment on other research trials. Patients must have: HIV positivity. Asymptomatic disease. CD4 count >= 50 cells/mm3 (CD4 count must be 50-499 cells/mm3 in patients receiving ddI plus vaccine or control, and must be >= 500 cells/mm3 in patients receiving vaccine or control only) [AS PER AMENDMENT 11/12/96: CD4 count >= 500 cells/mm3 for stratum 1 patients and 200-400 for stratum 2 patients]. HLA A2 positive documentation. An Epstein Barr virus B cell line established within 90 days prior to study entry. Consent of parent or guardian if less than 18 years of age. NOTE: Study is NOT approved for prisoner participation. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Medical contraindication to study participation or inability to comply with study requirements. Grade 2 or worse peripheral neuropathy (applicable only to patients receiving ddI plus vaccine or control). Concurrent Medication: Excluded: Immunomodulating agents, such as inosiplex, ditiocarb sodium, lithium, interferons, interleukin-2, and systemic steroids. Any antiretroviral therapy that may increase the risk of peripheral neuropathy (e.g., stavudine, zalcitabine [AS PER AMENDMENT 11/12/96: e.g., zalcitabine or lamivudine]). Agents such as IV pentamidine that may increase the risk of pancreatitis. Standard of care vaccines (in patients receiving vaccine) [AS PER AMENDMENT 11/12/96: Standard of care immunizations are permitted 60 days before Schedule 1 vaccine therapy and during Schedule 2 vaccine therapy (but not within 2 weeks of study immunization)]. AS PER AMENDMENT 11/12/96: Rifabutin, disulfiram (antabuse), or other medication with similar effects, including metronidazole. 6.AS PER AMENDMENT 11/12/96: The following are prohibited in patients receiving ritonavir: amiodarone, astemizole, bepridil, bupropion, cisapride, clozapine, encainide, flecainide, meperidine, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, terfenadine, alprazolam, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, and zolpidem. Patients with the following prior conditions are excluded: History of grade 2 or worse liver abnormality. Known allergy to vaccine components. Chronic diarrhea persisting for 4 or more weeks within 30 days prior to study entry. History of pancreatitis (applicable only to patients receiving ddI plus vaccine or control). [AS PER AMENDMENT 11/12/96: History of chronic pancreatitis or history of acute pancreatitis within 2 years prior to entry (stratum 2 patients only).] Prior Medication: Excluded: Any prior anti-HIV vaccines. Excluded within 90 days prior to study entry: Immunomodulating agents, such as Inosiplex, ditiocarb sodium, lithium, interferons, interleukin-2, and systemic steroids. Any antiretroviral therapy that may increase the risk of peripheral neuropathy (e.g., stavudine, zalcitabine [AS PER AMENDMENT 11/12/96: e.g., zalcitabine or lamivudine]). Agents such as IV pentamidine that may increase the risk of pancreatitis. Any treatment for an AIDS-defining illness (applicable ONLY to patients in the stratum receiving ddI plus vaccine or control). Excluded within 6 months prior to study entry: Any other antiretrovirals or immunomodulators besides those mentioned above. Allergy desensitization or other vaccines [AS PER AMENDMENT 11/12/96: excluded within 60 days prior to entry].

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ritonavir|nan|
|Biological: gp160 Vaccine (Immuno-AG)|nan|
|Drug: Stavudine|nan|
|Drug: Didanosine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccines, Synthetic, Didanosine, Drug Therapy, Combination, HIV Envelope Protein gp160, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Stavudine, HIV Protease Inhibitors, AIDS Vaccines, Ritonavir, Reverse Transcriptase Inhibitors, HIV Therapeutic Vaccine