OBJECTIVE: 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. DESIGN: Prospective study during a 2.5-year follow-up period; cohort study with pairwise matched controls. SETTING: The Amsterdam cohort study on the course of 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 progression. In addition, 45 men with a defined moment of appearance of SI variants and 45 matched controls without SI variants were compared for CD4+ cell decline. MEASUREMENTS: Syncytium-inducing variants were detected 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 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% Cl, 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 x 10(9)/L(Cl, 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 x 10(9)/L; 95% Cl, 0.05 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 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.
OBJECTIVE: 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. DESIGN: Prospective study during a 2.5-year follow-up period; cohort study with pairwise matched controls. SETTING: The Amsterdam cohort study on the course of HIV-1 infection in homosexual men. PARTICIPANTS: Asymptomatic HIV-1 infectedmen (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 and 45 matched controls without SI variants were compared for CD4+ cell decline. MEASUREMENTS: Syncytium-inducing variants were detected 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 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% Cl, 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 x 10(9)/L(Cl, 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 x 10(9)/L; 95% Cl, 0.05 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 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.
Authors: R D Berkowitz; A B van't Wout; N A Kootstra; M E Moreno; V D Linquist-Stepps; C Bare; C A Stoddart; H Schuitemaker; J M McCune Journal: J Virol Date: 1999-09 Impact factor: 5.103
Authors: T Beaumont; S Broersen; A van Nuenen; H G Huisman; A M de Roda Husman; J L Heeney; H Schuitemaker Journal: J Virol Date: 2000-09 Impact factor: 5.103
Authors: H Blaak; A B van't Wout; M Brouwer; B Hooibrink; E Hovenkamp; H Schuitemaker Journal: Proc Natl Acad Sci U S A Date: 2000-02-01 Impact factor: 11.205
Authors: Catherine N Kibirige; Frederick A Menendez; Hao Zhang; Tricia L Nilles; Susan Langan; Joseph B Margolick Journal: Med Hypotheses Date: 2014-04-13 Impact factor: 1.538
Authors: A B van't Wout; N A Kootstra; G A Mulder-Kampinga; N Albrecht-van Lent; H J Scherpbier; J Veenstra; K Boer; R A Coutinho; F Miedema; H Schuitemaker Journal: J Clin Invest Date: 1994-11 Impact factor: 14.808