HIV Infections
Conditions
Keywords
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
Brief summary
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
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).
Interventions
Sponsors
Bristol-Myers Squibb
Immuno-US
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
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 \[AS PER AMENDMENT 11/12/96: * excluded within 60 days prior to entry\].
Countries
United States
Outcome results
None listed