LEUKOCYTE ADHESION MOLECULES AS A COFACTOR IN AIDS - BASIC SCIENCE AND PILOT-STUDY

It is well known that the AIDS pandemic is a consequence of pandemic H IV infection. However, Koch's postulates are not satisfied for two rea sons: 1) AIDS cannot be experimentally produced in animals susceptible to HIV infection and 2) some people have AIDS (idiopathic CD4(+) T ly mphocytopenia) in the absence of HIV infection. It follows that there is a human immunologic cofactor (HIC) that causes AIDS when certain ot her conditions are satisfied, and the most common of these other condi tions (but not the only one) is HIV infection. Results from microbiolo gy make leukocyte adhesion molecules a good candidate for the HIC. We have tested this hypothesis with a pilot study in which a small number of patients with HIV disease were infused with a monoclonal mouse ant ibody (MmAb) directed against an LFA-1 adhesion epitope, and then with F(ab) and F(ab)(2)' fragments that bind to the same epitope but are n onimmunogenic. Both agents reduced peripheral viral burden significant ly but fragments were more effective in this respect than the MmAb due to the mitogenic properties of the latter. For the same reason, only the MmAb were highly effective in raising circulating levels of single and double-marked CD4(+) T lymphocytes, with a correlated resolution of cutaneous anergy.