The Impact of the Syncytium-Inducing Phenotype of Human Immunodeficiency Virus on Disease Progression

Many patients infected with human immunodeficiency virus (HIV) yield syncytium-inducing (SI) virus isolates that are cytopathic in cell culture. The presence of SI virus was assessed in 325 persons entering 11 antiretroviral therapy trials and correlated with both CD4 cell declines and clinical end points. Adjusted mean rates of CD4 cell count decline were 40 and 102 cells/year in the non-SI (NSI) and SI groups, respectively (P < .0001). Rates of decline in 16 persons converting from NSI to SI virus averaged 31 cells/year before conversion and 142 cells/year afterward (P = .04). In a nested case-control analysis, persons who experienced surrogate marker end points or opportunistic infections were 2.3-3.5 times more likely to have SI virus than were controls (P = .01-.04) but who died were similar to controls with respect to virus phenotype (P = .70). Presence of the SI phenotype of HIV is a strong predictor of decline in CD4 cell count and progression of disease; however, controlling for the CD4 cell count, the SI phenotype did not increase the immediate risk of death.