Relations among CD4 Lymphocyte Count Nadir, Antiretroviral Therapy, and HIV-1 Disease Progression: Results from the EuroSIDA Study

  1. Veronica Miller, PhD;
  2. Amanda Mocroft, PhD;
  3. Peter Reiss, MD;
  4. Christine Katlama, MD;
  5. Anthony I. Papadopoulos, MD;
  6. Terese Katzenstein, MD;
  7. Jan van Lunzen, MD;
  8. Francisco Antunes, MD;
  9. Andrew N. Phillips, PhD;
  10. Jens D. Lundgren, MD; and
  11. for the EuroSIDA Study Group*
  1. From J.W. Goethe-Universität, Zentrum der Inneren Medizin, Frankfurt, Germany, and Universitätsklinikum Eppendorf, Hamburg, Germany; Royal Free Centre for HIV Medicine, London, United Kingdom; Academic Medical Center, Amsterdam, the Netherlands; Hôpital de la Pitiè-Salpêtière, Paris, France; 1st IKA Hospital, Athens, Greece; Rigshospitalet and Hvidovre University Hospital, Copenhagen, Denmark; and Hospital Santa Maria, Lisbon, Portugal.

    Abstract

    Background: The effect of previous CD4 cell count nadir on clinical progression in patients with increases in CD4 cell counts has not been investigated.

    Objective: To assess risk for progression of HIV disease in patients with CD4 counts of at least 200 cells/mm3 (stratified by the lowest previous CD4 count) and compare the rate of progression in patients with CD4 counts less than 50 cells/mm3 with that in patients whose CD4 counts rebounded from less than 50 cells/mm3 to at least 200 cells/mm3.

    Design: Prospective, observational multicenter study.

    Setting: 52 HIV outpatient clinics in Europe.

    Patients: Two groups were identified: those with CD4 counts of at least 200 cells/mm3 (group A) and those with CD4 counts less than 50 cells/mm3 (group B). Group A was stratified according to the lowest previous CD4 count: at least 150 cells/mm3 (stratum 1), 100 to 149 cells/mm3 (stratum 2), 50 to 99 cells/mm3 (stratum 3), and 1 to 50 cells/mm3 (stratum 4).

    Measurements: Patients were followed until a progression event occurred (first AIDS-defining event, new AIDS-defining event, or death) or until the CD4 count decreased to less than 200 cells/mm3 (group A) or increased to more than 50 cells/mm3 (group B). Incidence rates were based on a patient-years analysis and reported as events per 100 patient-years of follow-up; the relative hazards for progression were based on Cox proportional-hazards models.

    Results: The overall rate of disease progression in group A was 3.9 per 100 patient-years (95% CI, 3.5 to 4.3 per 100 patient-years), whereas in group B it was much higher (72.9 per 100 patient-years [CI, 69.0 to 76.8 per 100 patient-years]). In group A, the rate increased in patients with previous low CD4 cell count nadirs, resulting in a significant increase in the relative hazard for progression. The relative hazards for strata 2, 3, and 4 were 2.29 (CI, 1.30 to 4.03), 3.65 (CI, 1.94 to 6.85), and 2.94 (CI, 1.44 to 6.00), respectively.

    Conclusions: Increases in CD4 counts from very low levels to at least 200 cells/mm3 are associated with a much reduced rate of disease progression. However, a previously low CD4 cell count nadir remains associated with a moderately higher risk for disease progression among patients with CD4 counts of at least 200 cells/mm3.

    *For members of the EuroSIDA Study Group, see Appendix.

    Article and Author Information

    • Grant Support: EuroSIDA is sponsored by the European Commission (BIOMED 1 [CT94-1637] and 2 [CT97-2713] programmes). Unrestricted educational grants have been received from GlaxoWellcome; Pharmacia & Upjohn; Roche Pharmaceuticals; and Merck, Sharpe, & Dohme.

    • Requests for Reprints: Veronica Miller, PhD, Klinikum der J.W. Goethe-Universität, Zentrum der Inneren Medizin, Infektionsambulanz Haus 68, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany; e-mail, miller{at}em.uni-frankfurt.de.

    • Current Author Addresses: Dr. Miller: J.W. Goethe-Universität, Zentrum der Inneren Medizin, Infektionsambulanz Haus 68, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.

    • Drs. Mocroft and Phillips: Royal Free Centre for HIV Medicine and Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, United Kingdom.

    • Dr. Reiss: NATEC Academic Medical Center, Meibergdreef 9, Room F5-108, 1105 AZ Amsterdam, the Netherlands.

    • Dr. Katlama: Department de Medicine Tropicale, Hôpital de la Pitiè-Salpêtriére, Boulevard de l'Hôpital 83, 75013 Paris, France.

    • Dr. Papadopoulos: 1st IKA Hospital Penteli, 15127 Athens, Greece.

    • Dr. Katzenstein: Department of Infectious Diseases, 7721 Rigshospitalet, Tagensvej, 2200 Copenhagen N, Denmark.

    • Dr. van Lunzen: Universitäts Klinikum Eppendorf, Zentrum der Inneren Medizin, Infektionsambulanz, Martinstrasse 52, 20246 Hamburg, Germany.

    • Dr. Antunes: Department of Infectious Diseases, Hospital Santa Maria, Avenue Professor Egas Moniz, 1600 Lisbon, Portugal.

    • Dr. Lundgren: Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, DK-2650 Hvidovre, Denmark.

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    1. Ann Intern Med April 6, 1999 vol. 130 no. 7 570-577
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