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 selected for either rapid or slow disease progression were evaluated. All 6 patients who developed AIDS within 5 years were initially infected with syncytiuminducing (SI) variants or showed a transition from non-SI-inducing (NSI) to SI variants. Detection of SI variants was associated with rapid decline of both CD8⁺ and CD4⁺ T cells. In contrast, the 6 slow progressors carried only NSI variants and maintained stable or increasing CD8⁺ T cell levels. The SI variants that were associated with initial infection were dual tropic, with efficient replication in primary macrophages and T cell lines. These results suggest that the ability to replicate in macrophages, rather than the SI or NSI phenotype 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.