PROGNOSTIC VALUE OF HIV-1 SYNCYTIUM-INDUCING PHENOTYPE FOR RATE OF CD4+ CELL DEPLETION AND PROGRESSION TO AIDS

Objective: To investigate the relation between detection of syncytium- inducing (SI), human immunodeficiency virus type 1 (HIV-1) variants, r ate of CD4+ cell decline, and clinical progression. Design: Prospectiv e study during a 2.5-year follow-up period; cohort study with pairwise matched controls. Setting: The Amsterdam cohort study on the course o f HIV-1 infection in homosexual men. Participants: Asymptomatic HIV-1- infected men (n = 225) were tested for the presence of SI variants and were studied prospectively for CD4+ cell decline and clinical progres sion. In addition, 45 men with a defined moment of appearance of SI va riants and 45 matched controls without SI variants were compared for C D4+ cell decline. Measurements: Syncytium-inducing variants were detec ted by cocultivation of peripheral blood mononuclear cells with the MT -2 T-cell line. Results: During a 30-month period, 70.8% of the men wi th SI variants progressed to AIDS, compared with 15.8% of men without SI variants at entry (P <0.0001). Multivariable Cox proportional hazar d analysis, controlling for CD4+ cell count and HIV-p24 antigenemia, s howed a relative hazard for SI variants of 6.7 (95% Cl, 3.5 to 12.7). In the matched control study, before the appearance of SI variants, CD 4+ cell counts of 45 men with SI variants and their controls were comp ared. Syncytium-inducing variants emerged at a mean CD4+ cell count of 0.48 x 10(9)/L (Cl, 0.42 to 0.54), coinciding with the onset of a thr eefold increased rate of CD4+ cell decline. Men developing AIDS with S I variants had decreased CD4+ cell counts (0.08 x 10(9)/L; 95% Cl, 0.0 5 to 0.12) at the time of diagnosis compared with persons progressing to AIDS without SI variants (0.25 x 10(9)/L; 95% Cl, 0.15 to 0.41) (P = 0.0035). Conclusions: The HIV-1 biological phenotype is a practical, binary marker for progression to AIDS, which is independent of decrea sed CD4+ cell counts and antigenemia. Appearance of SI variants, occur ring 2 years before progression to AIDS on the average, is predictive for a significantly increased rate of CD4+ cell decline.