title: Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS.
abstract: 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.
  
  
  METHODS
  Prospective study during a 2.5-year follow-up period; cohort study with pairwise matched controls.
  
  
  METHODS
  The Amsterdam cohort study on the course of HIV-1 infection in homosexual men.
  
  
  METHODS
  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.
  
  
  METHODS
  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.affiliation: Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
authors.forename: M
authors.initials: M
authors.lastname: Koot
authors.forename: I P
authors.initials: IP
authors.lastname: Keet
authors.forename: A H
authors.initials: AH
authors.lastname: Vos
authors.forename: R E
authors.initials: RE
authors.lastname: de Goede
authors.forename: M T
authors.initials: MT
authors.lastname: Roos
authors.forename: R A
authors.initials: RA
authors.lastname: Coutinho
authors.forename: F
authors.initials: F
authors.lastname: Miedema
authors.forename: P T
authors.initials: PT
authors.lastname: Schellekens
authors.forename: M
authors.initials: M
authors.lastname: Tersmette
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D002460:Cell Line; D015331:Cohort Studies; D015726:Giant Cells / Q000382:microbiology*; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D015994:Incidence; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies