a study to evaluate the effects of interleukin-12 (rhil-12) in hiv-positive patients with cd4 cell counts less than 50 cells/mm3 or 300-500 cells/mm3

Conditions: HIV Infections

Summary: the purpose of this study is to determine the tolerance and effectiveness of rhil-12 in hiv-positive patients with cd4 cell counts less than 50 cells/mm3 versus 300-500 cells/mm3. this study will look at the ability of rhil-12 to boost the immune system against hiv and hiv-associated bacterial infections in these patients. il-12 is found naturally in the body and rhil-12 is the commercially produced version. il-12 may enhance anti-hiv immune system activity by increasing the number of cells that fight infection. il-12 may also increase the body's ability to fight bacterial infections such as mycobacterium avium complex (mac).

il-12 has a number of effects in vitro that could be relevant to hiv disease including promotion of th1 cell development, enhancement of hiv-specific t cell responses in cells from subjects with aids, and, of particular relevance to mac disease, increasing secretion of cytotoxic cytokines such as ifn-gamma from both t lymphocytes and nk cells. part a (36 patients with less than 50 cd4+ cells/mm3): patients are randomized within one of three sequential dose cohorts and receive either rhil-12 or matching placebo by subcutaneous injection twice weekly for four weeks. eligible patients will participate in only 1 of the 3 dosing cohorts. dose escalation to a new cohort of patients in part a will occur only if all 3 of the following occur: (1) at least 9 patients in the rhil-12 arm have been enrolled in the current dose group and have either been on study drug for at least 4 weeks (temporary discontinuation is allowed) or have permanently discontinued study drug due to a primary toxicity endpoint. \[(2) as per amendment 6/16/97: fewer than 2 of the 12 patients receiving rhil-12 at 30 or 100 ng/kg have had a primary toxicity endpoint.\] (3) adequate data from a genetics institute/wyeth ayerst-sponsored dose escalation trial have been obtained and analyzed to demonstrate the safety of the dose to be administered to the next cohort. note: if 3 or more patients in the rhil-12 arm of a given dose in part a experience a primary toxicity endpoint, then accrual and further drug administration will be discontinued. \[as per amendment 6/16/97: if a cohort has exactly two patients in the rhil-12 arm that experience a primary toxicity endpoint, then the next cohort receives study drug at the same dose as the current cohort, but administered only once a week. if a cohort receiving study drug administered once a week has at least two subjects experience a primary toxicity endpoint, then further drug administration in part a is stopped. any cohort that receives study drug once a week is the last cohort in part a; no further dose escalation is performed\]. part b (18 subjects with 300-500 cd4+ cells/mm3): patients are randomized to receive either the maximum tolerated dose (determined in part a) of rhil-12 or matching placebo subcutaneously twice a week for 4 weeks. \[as per amendment 01/29/99: because of slow accrual for cohort 3 of part a, concurrent enrollment will begin for part b while cohort 3 of part a is completed. there will be no further dose escalation in part a. part a will remain open to accrual until the final enrollee to part b completes 4 weeks of study treatment. for part b, 27 patients will be randomized with equal probability to one of two rhil-12 doses or placebo. semiweekly injections are given for 4 weeks.\]

Eligibility criteria:
inclusion criteria you may be eligible for this study if you: * are hiv-positive. * are 18-60 years old. * have a cd4 count less than 50 cells/mm3 or between 300-500 cells/mm3 within 30 days of study entry. * are expected to live at least 12 weeks. * agree to practice abstinence or use effective methods of birth control during the study. exclusion criteria you will not be eligible for this study if you: * have a history of cytomegalovirus (cmv) end-organ disease. * have a history of invasive fungal disease, unless the condition has been stable for 2 months. * have a history of severe allergic reactions to il-2 or il-12. * have a history of heart problems, autoimmune or rheumatologic disease, gastrointestinal bleeding, or any condition that would keep you from completing the study. * have mac-related symptoms (fever, weight loss, frequent diarrhea) for at least 2 months prior to study entry. * are enrolled in another experimental research treatment study. * abuse alcohol or drugs. * are pregnant or breast-feeding.

Keywords: recombinant proteins t-lymphocytes dose-response relationship, drug mycobacterium avium complex cd4 lymphocyte count interleukin-12 killer cells, natural th1 cells interferon type ii