Leukocyte adhesion molecules as a cofactor in AIDS: basic science and pilot study

Abstract

It is well known that the AIDS pandemic is a consequence of pandemic HIV infection. However, Koch's postulates are not satisfied for two reasons: 1) AIDS cannot be experimentally produced in animals susceptible to HIV infection and 2) some people have AIDS (idiopathic CD4+ T lymphocytopenia) in the absence of HIV infection. It follows that there is a human immunologic cofactor (HIC) that causes AIDS when certain other conditions are satisfied, and the most common of these other conditions (but not the only one) is HIV infection. Results from microbiology 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 antibody (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 nonimmunogenic. Both agents reduced peripheral viral burden significantly 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.