Prognostic Value of HIV-1 Syncytium-Inducing Phenotype for Rate of CD4+ Cell Depletion and Progression to AIDS

  1. Maarten Koot, MSc;
  2. Ireneus P. M. Keet, MD;
  3. Aster H. V. Vos;
  4. Ruud E. Y. de Goede, BSc;
  5. Marijke Th. L. Roos, BSc;
  6. Roel A. Coutinho, MD, PhD;
  7. Frank Miedema, PhD;
  8. Peter Th. A. Schellekens, MD, PhD; and
  9. Matthijs Tersmette, MD, PhD
  1. From the Netherlands Red Cross Blood Transfusion Service, the University of Amsterdam, Amsterdam, The Netherlands; the Municipal Health Service, Amsterdam, The Netherlands. Requests for Reprints: M. Tersmette, MD, PhD, Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, P.O. Box 9406, 1006 AK Amsterdam, The Netherlands. Acknowledgments: The authors thank M. Bakker and N. Albrecht van Lent for technical assistance, Drs. W. Schaasberg and C. Kuiken for statistical analysis, and Drs. G.J.A. Offerhaus and H. Schuitemaker for critically reading the manuscript; as well as thank MRC AIDS Research Project, Hertfordshire, United Kingdom, for providing the MT-2 cells. Grant Support: By RGO/WVC (Ministry of Public Health, no. 90016) and the Netherlands Foundation of Preventive Medicine (28-1079). Dr. Frank Miedema is a senior fellow of the Royal Netherlands Academy of Art and Sciences.

    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.

    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 and45 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% 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).

    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.

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    1. Ann Intern Med May 1, 1993 vol. 118 no. 9 681-688
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