Safe Interruption of Maintenance Therapy against Previous Infection with Four Common HIV-Associated Opportunistic Pathogens during Potent Antiretroviral Therapy

  1. Ole Kirk, MD;
  2. Peter Reiss, MD;
  3. Caterina Uberti-Foppa, MD;
  4. Markus Bickel, MD;
  5. Jan Gerstoft, MD;
  6. Christian Pradier, MD;
  7. Ferdinand W. Wit, MD;
  8. Bruno Ledergerber, PhD;
  9. Jens D. Lundgren, MD;
  10. Hansjakob Furrer, MD; and
  11. for Seven European HIV Cohorts*
  1. From Hvidovre Hospital, University of Copenhagen, Hvidovre, and Rigshospitalet, Copenhagen, Denmark; Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; San Raffaele Hospital, Milan, Italy; J.W. Goethe University Clinic, Frankfurt, Germany; Hôpital l'Archet, Nice, France; University Hospital Zurich, Zurich, Switzerland; and University Hospital Bern, Bern, Switzerland.

    Abstract

    Background: The safety of interrupting maintenance therapy for previous opportunistic infections other than Pneumocystis carinii pneumonia among patients with HIV infection who respond to potent antiretroviral therapy has not been well documented.

    Objective: To assess the safety of interrupting maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy.

    Design: Observational study.

    Setting: Seven European HIV cohorts.

    Patients: 358 patients taking potent antiretroviral therapy (≥ 3 drugs) who interrupted maintenance therapy at a CD4 lymphocyte count greater than 50 × 106 cells/L.

    Measurements: Recurrence of opportunistic infection after interruption of maintenance therapy.

    Results: 379 interruptions of maintenance therapy were identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte count was less than 100 × 106 cells/L or when only one recent measurement exceeded this value. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted once CD4 counts were greater than 100 × 106 cells/L for 10 and 8 months, respectively. One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 × 106 cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% CI, 0.07 to 1.95 per 100 person-years), 0.90 per 100 person-years (CI, 0.11 to 3.25 per 100 person-years), 0.84 per 100 person-years (CI, 0.02 to 4.68 per 100 person-years), and 0.00 per 100 person-years (CI, 0.00 to 5.27 per 100 person-years), respectively.

    Conclusion: Maintenance therapy against previous infection with CMV, MAC, Toxoplasma gondii, or Cryptococcus neoformans in patients with HIV infection can be interrupted after sustained CD4 count increases to greater than 200 (or possibly 100 to 200) × 106 cells/L for at least 6 months after the start of potent antiretroviral therapy.

    *For members of the participating European HIV cohorts, see the Appendix.

    Article and Author Information

    • Grant Support: The EuroSIDA study was supported by grants from the European Commission BIOMED 1 (CT94-1637) and BIOMED 2 (CT97-2713) programs and the fifth framework program (QLK2-2000-00773); from GlaxoSmithKline, Roche, and Boehringer-Ingelheim; and from the Swiss Federal Office for Education and Science (Swiss sites only). The Swiss HIV Cohort Study was supported by grant 3345-062041 from the Swiss National Science Foundation. The AIDS Therapy Evaluation Project Netherlands was supported by grant CURE/97-46486 from the Health Insurance Fund Council, Amstelveen, the Netherlands. The Frankfurt HIV Cohort was supported by grants from the Bundesministerium für Bildung und Forschung (BMBF 01KI9406/6 and 01KI9718) and GlaxoSmithKline Research.

    • Requests for Single Reprints: Ole Kirk, MD, Coordinating Centre of EuroSIDA, Department of Infectious Diseases, Hvidovre University Hospital, Kettegaard Alle, 2650 Hvidovre, Denmark; e-mail, oki{at}cphiv.dk.

    • Current Author Addresses: Drs. Kirk and Lundgren: Coordinating Centre of EuroSIDA, Department of Infectious Diseases, Hvidovre University Hospital, Kettegaard Alle, 2650 Hvidovre, Denmark.

    • Drs. Reiss and Wit: Academic Medical Center, University of Amsterdam, Division of Infectious Diseases, Tropical Medicine, and AIDS, and National AIDS Therapy Evaluation Center, Amsterdam, The Netherlands.

    • Dr. Uberti-Foppa: San Raffaele Hospital, Infectious Diseases Department, Milan, Italy.

    • Dr. Bickel: J.W. Goethe University Clinic, Department of Infectious Diseases, Frankfurt, Germany.

    • Dr. Gerstoft: Rigshospitalet, Department of Infectious Diseases, Copenhagen, Denmark.

    • Dr. Pradier: Hopital l'Archet, Tropical and Infectious Diseases Department, Nice, France.

    • Dr. Ledergerber: University Hospital Zürich, Division of Infectious Diseases and Hospital Epidemiology, Zürich, Switzerland.

    • Dr. Furrer: University Hospital Bern, Division of Infectious Diseases, Bern, Switzerland.

    • Author Contributions: Conception and design: O. Kirk, P. Reiss, B. Ledergerber, J.D. Lundgren, H. Furrer.

    • Analysis and interpretation of the data: O. Kirk, B. Ledergerber, J.D. Lundgren, H. Furrer.

    • Drafting of the article: O. Kirk, B. Ledergerber, J.D. Lundgren, H. Furrer.

    • Critical revision of the article for important intellectual content: O. Kirk, P. Reiss, J.D. Lundgren, H. Furrer.

    • Final approval of the article: O. Kirk, P. Reiss, C. Uberti-Foppa, M. Bickel, J. Gerstoft, C. Pradier, F.W. Wit, B. Ledergerber, J.D. Lundgren, H. Furrer.

    • Provision of study materials or patients: O. Kirk, P. Reiss, C. Uberti-Foppa, M. Bickel, J. Gerstoft, C. Pradier, F.W. Wit, H. Furrer.

    • Statistical expertise: O. Kirk, B. Ledergerber.

    • Obtaining of funding: O. Kirk, J.D. Lundgren, H. Furrer.

    • Administrative, technical, or logistic support: O. Kirk, B. Ledergerber, H. Furrer.

    • Collection and assembly of data: O. Kirk, C. Uberti-Foppa, M. Bickel, C. Pradier, F.W. Wit, H. Furrer.

    Summary for Patients

    • Summaries for Patients:Can Maintenance Therapy for Opportunistic Infections in HIV-Infected People Be Stopped Safely? Ann Intern Med August 20, 2002 137:I-34
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    1. Ann Intern Med August 20, 2002 vol. 137 no. 4 239-250
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