INHIBITION OF SYNCYTIA-INDUCING (SI) VIRUS BY AUTOLOGOUS SERUM FROM HIV-1-INFECTED INDIVIDUALS

Background: Progression from HIV infection to AIDS is often accompanie d or even predicted by a switch of the virus to a more pathogenic or s yncytia-inducing (SI) phenotype concomitant with the development of HI V variants escaping neutralizing antibodies. Objective: Here we studie d the capacity of sera to neutralize autologous SI-HIV or the laborato ry strain III, and compared these data to the viral load in HIV-l-infe cted patients. Methods: The SI phenotype of HIV was detected by co-cul tivation of peripheral blood mononuclear cells (PBMCs) with MT2 cells in 112 patients stratified by their CD4 cell counts. Sera at dilutions of 1:15 and 1:75 were added to MT2 co-cultures with autologous PBMCs as well as with HIV-1/IIIB-infected H9 cells to study the inhibitory c apacity. The p24 antigenemia was detected by enzyme-linked immunosorbe nt assay (ELISA) and the circulating HIV RNA was determined using the polymerase chain reaction (PCR). Results: The SI virus was detected in PBMCs from 31/65 patients with less than or equal to 200 CD4+ cells, 8/28 patients with 201-499 CD4(+) cells, and 1/19 patients with greate r than or equal to 500 CD4(+) cells. Sera from 16/40 patients inhibite d the autologous SI-HIV. In sera from patients with less than or equal to 200 CD4(+) cells, p24 antigen could be detected in 17/34 (50%) pat ients with non-syncytia-inducing (NSI) phenotype and in 7/19 (37%) pat ients carrying SI-HIV without serum inhibition. In contrast, all 12 se ra with inhibitory activity to the autologous SI-HIV were negative for p24 antigen. A similar tendency was seen in patients with higher CD4( +) T-cell counts. The mean load of circulating HIV RNA did not differ among groups of patients. Independently of their neutralizing activity to the autologous SI virus, the majority of sera were able to neutral ize the laboratory HIV-1/IIIB. Conclusions: While most of the patients ' sera neutralized the laboratory HIV-1/IIIB strain, only some sera we re able to inhibit the autologous SI-HIV. In these cases, the detectab le SI-HIV may still be controlled by the immune system in vivo, which is consistent with a low p24 antigenemia.