PITFALLS IN THE USE OF SURROGATE MARKERS FOR HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE - FURTHER EVIDENCE ON PATHOGENESIS

The administration of drugs to human immunodeficiency virus patients w ith a pronounced CD4(+) T lymphocytopenia may cause non-specific bindi ng of the murine antibodies used in flow cytometry. This has produced spurious reports of early thymocytes in the circulating blood of human immunodeficiency virus-infected individuals following treatment with an anti-adhesion monoclonal mouse antibody (Cytolin(+)). Recent clinic al experience with Cytolin(+) confirms the pathogenic role of leukocyt e adhesion pathways in human immunodeficiency virus infection. However , this experience also illustrates how comparisons of viral burden can be misleading. For nine patients with low CD4 counts, Cytolin(+) alon e reduced the mean ribonucleic acid-polymerase chain reaction by 0.45 log to 39 800 particles per mt. Ten patients with more advanced diseas e added Cytolin(+) to an established regimen of standard antiretrovira l drugs. Their mean polymerase chain reaction was only reduced by 0.2 log to 91 501. Yet, 67% of the former patients experienced a major cli nical event within seven months, whereas the latter patients remained stable during this time.