Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS

Ann Intern Med. 1993 May 1;118(9):681-8. doi: 10.7326/0003-4819-118-9-199305010-00004.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / microbiology
  • Adult
  • CD4-Positive T-Lymphocytes*
  • Cell Line
  • Cohort Studies
  • Giant Cells / microbiology*
  • HIV Infections / immunology*
  • HIV Infections / microbiology*
  • HIV-1 / pathogenicity*
  • Humans
  • Incidence
  • Leukocyte Count
  • Male
  • Middle Aged
  • Phenotype
  • Prevalence
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies