INFECTION WITH DUAL-TROPIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VARIANTS ASSOCIATED WITH RAPID TOTAL T-CELL DECLINE AND DISEASE PROGRESSION IN INJECTION-DRUG USERS

The characteristics of sequential human immunodeficiency virus type 1 (HIV-1) isolates from 12 seroconverters among injection drug users sel ected for either rapid or slow disease progression were evaluated. All 6 patients who developed AIDS within 5 years were initially infected with syncytium-inducing (SI) variants or showed a transition from non- SI-inducing (NSI) to SI variants. Detection of SI variants was associa ted with rapid decline of both CD8(+) and CD4(+) T cells. In contrast, the 6 slow progressors carried only NSI variants and maintained stabl e or increasing CD8(+) T cell levels. The SI variants that were associ ated with initial infection were dual tropic, with efficient replicati on in primary macrophages and T cell lines. These results suggest that the ability to replicate in macrophages, rather than the SI or NSI ph enotype per se, may be an important determinant of HIV-1 transmission and that dual-tropic viruses, when transmitted, may be associated with rapid progression to AIDS.