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: HIV Infections

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.

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).

Eligibility criteria:
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 \[as per amendment 11/12/96: * excluded within 60 days prior to entry\].

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