Maarten Koot, MSc; Ireneus P. M. Keet, MD; Aster H. V. Vos; Ruud E. Y. de Goede, BSc; Marijke Th. L. Roos, BSc; Roel A. Coutinho, MD, PhD; Frank Miedema, PhD; Peter Th. A. Schellekens, MD, PhD; Matthijs Tersmette, MD, PhD
To investigate the relation between detection of syncytium-inducing (SI), human immunodeficiency virus type 1 (HIV-1) variants, rate of CD4+ cell decline, and clinical progression.
Prospective study during a 2.5-year follow-up period; cohort study with pairwise matched controls.
The Amsterdam cohort study on the course of HIV-1 infection in homosexual men.
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 progression. In addition, 45 men with a defined moment of appearance of SI variants and45 matched controls without SI variants were compared for CD4+ cell decline.
Syncytium-inducing variants were detected by cocultivation of peripheral blood mononuclear cells with the MT-2 T-cell line.
During a 30-month period, 70.8% of the men with SI variants progressed to AIDS, compared with 15.8% of men without SI variants at entry (P<0.0001). Multivariable Cox proportional-hazard analysis, controlling for CD4+ cell count and HIV-p24 antigenemia, showed a relative hazard for SI variants of 6.7 (95% CI, 3.5 to 12.7). In the matched control study, before the appearance of SI variants, CD4+ cell counts of 45 men with SI variants and their controls were compared. Syncytium-inducing variants emerged at a mean CD4+ cell count of 0.48 109/L (CI, 0.42 to 0.54), coinciding with the onset of a threefold increased rate of CD4+ cell decline. Men developing AIDS with SI variants had decreased CD4+ cell counts (0.08 109/L; 95% CI, 0.05 to 0.12) at the time of diagnosis compared with persons progressing to AIDS without SI variants (0.25 109/L; 95% CI, 0.15 to 0.41) (P = 0.0035).
The HIV-1 biological phenotype is a practical, binary marker for progression to AIDS, which is independent of decreased CD4+ cell counts and antigenemia. Appearance of SI variants, occurring 2 years before progression to AIDS on the average, is predictive for a significantly increased rate of CD4+ cell decline.
Koot M, Keet IPM, Vos AHV, de Goede REY, Roos MTL, Coutinho RA, et al. Prognostic Value of HIV-1 Syncytium-Inducing Phenotype for Rate of CD4+ Cell Depletion and Progression to AIDS. Ann Intern Med. 1993;118:681–688. doi: 10.7326/0003-4819-118-9-199305010-00004
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Published: Ann Intern Med. 1993;118(9):681-688.
HIV, Infectious Disease.
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