Successful Discontinuation of Therapy for Disseminated Mycobacterium avium Complex Infection after Effective Antiretroviral Therapy

  1. Stephen D. Shafran, MD;
  2. Laura D. Mashinter, BScN, RN;
  3. Peter Phillips, MD;
  4. Richard G. Lalonde, MD;
  5. M. John Gill, MB;
  6. Sharon L. Walmsley, MD;
  7. Emil Toma, MD;
  8. Brian Conway, MD;
  9. Ignatius W. Fong, MB;
  10. Anita R. Rachlis, MD;
  11. Kurt E. Williams, MD;
  12. Gary E. Garber, MD;
  13. Walter F. Schlech III, MD; and
  14. Fiona Smaill, MB, ChB
  1. From the University of Alberta, Edmonton, Alberta; University of British Columbia, Vancouver, British Columbia; McGill University and University of Montreal, Montreal, Quebec; University of Calgary, Calgary, Alberta; University of Toronto, Toronto, Ontario; University of Saskatchewan, Saskatoon, Saskatchewan; University of Ottawa, Ottawa, Ontario; Dalhousie University, Halifax, Nova Scotia; and McMaster University, Hamilton, Ontario, Canada.

    Abstract

    Background: Highly active antiretroviral therapy (HAART) is associated with improvement or resolution of several HIV-associated opportunistic infections. Although prophylaxis against disseminated Mycobacterium avium complex infection may be successfully discontinued after a favorable response to HAART, the 1999 guidelines from the U.S. Public Health Service/Infectious Diseases Society of America recommend continuing therapy for disseminated M. avium complex infection, regardless of the response to HAART.

    Objective: To examine the outcome among patients with disseminated M. avium complex infection whose antimycobacterial therapy was discontinued after a favorable response to HAART.

    Design: Retrospective chart review between May 2000 and May 2001.

    Setting: 13 Canadian HIV clinics.

    Patients: 52 HIV-infected adults (43 men; mean age, 37.3 years) in whom successful antimycobacterial therapy for disseminated M. avium complex infection was discontinued after a favorable virologic response to HAART.

    Measurements: Survival, survival free of disseminated M. avium complex infection, and CD4+ cell count responses.

    Results: At the time of diagnosis of disseminated M. avium complex infection, the median CD4+ cell count was 0.016 × 109 cells/L, and the median plasma HIV RNA level was 90 000 copies/mL (plasma HIV RNA levels were available for only 21 patients). The patients received a median of 32 months of antimycobacterial therapy that included ethambutol plus either clarithromycin or azithromycin. When antimycobacterial therapy was discontinued, the median CD4+ cell count was 0.23 × 109 cells/L and the median plasma HIV RNA level was less than 50 copies/mL. A median of 20 months after discontinuation of antimycobacterial therapy, only 1 patient had developed recurrent M. avium complex disease (37 months after stopping antimycobacterial therapy). This patient had stopped HAART 2 months earlier because of uncontrolled HIV viremia. Twenty months after stopping antimycobacterial therapy, the other 51 patients had a median CD4+ cell count of 0.288 × 109 cells/L; 34 (67%) had undetectable plasma HIV RNA levels, and 8 (15%) had plasma HIV RNA levels of 50 to 1000 copies/mL.

    Conclusions: Discontinuation of successful disseminated M. avium complex therapy after a successful response to HAART is safe and reduces patients' pill burdens, potential drug adverse effects, drug interactions, and costs of therapy.

    Article and Author Information

    • Note: Since the acceptance of this manuscript, a large European cohort also demonstrated the safety of discontinuing maintenance antimycobacterial therapy for Mycobacterium avium infection ( Kirk O, Reiss P, Uberti-Foppa C, Bickel M, Gerstoft J, Pradier C, et al. Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy. Ann Intern Med. 2002; 137:239-50. [PMID: 12186514] KirkO ReissP Uberti-FoppaC BickelM GerstoftJ PradierC et al.

      Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy

      Ann Intern Med 2002 239-50 ).

    • Requests for Single Reprints: Stephen D. Shafran, MD, Division of Infectious Diseases, University of Alberta Hospital, 8440 112 Street, WMC 2E4.16, Edmonton, Alberta T6G 2B7, Canada; e-mail, shafran{at}uah.ualberta.ca.

    • Current Author Addresses: Dr. Shafran and Ms. Mashinter: Division of Infectious Diseases, WMC 2E4.11, University of Alberta Hospital, 8440 112 Street, Edmonton, Alberta T6G 2B7, Canada.

    • Dr. Phillips: St. Paul's Hospital, 667–1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada.

    • Dr. Lalonde: McGill University Health Centre (Montreal Chest Institute), 3650 Saint-Urbain Street, Montreal, Quebec H2X 2P4, Canada.

    • Dr. Gill: Division of Infectious Diseases, University of Calgary, 3330 Hospital Drive, Calgary, Alberta T2N 4N1, Canada.

    • Dr. Walmsley: Toronto General Hospital, 200 Elizabeth Street, Eaton Wing, Ground Floor, Room 219, Toronto, Ontario M5G 2C4, Canada.

    • Dr. Toma: Centre Hôpital Université de Montreal-Hôtel Dieu, 3840 rue Saint-Urbain, Montreal, Quebec H2W 1T8, Canada.

    • Dr. Conway: Department of Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.

    • Dr. Fong: St. Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada.

    • Dr. Rachlis: Sunnybrook and Women's College HSC, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.

    • Dr. Williams: Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan S7N 0W8, Canada.

    • Dr. Garber: The Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.

    • Dr. Schlech: Queen Elizabeth II Health Science Center, 1278 Tower Road, Halifax, Nova Scotia B3H 2Y9, Canada.

    • Dr. Smaill: McMaster University Health Science Center, 1200 Main Street, Hamilton, Ontario L8S 4J9, Canada.

    • Author Contributions: Conception and design: S.D. Shafran, M.J. Gill, B. Conway.

    • Analysis and interpretation of the data: S.D. Shafran, L.D. Mashinter, R.G. Lalonde, M.J. Gill, B. Conway.

    • Drafting of the article: S.D. Shafran, R.G. Lalonde, B. Conway, K.E. Williams, G.E. Garber.

    • Critical revision of the article for important intellectual content: S.D. Shafran, L.D. Mashinter, P. Phillips, M.J. Gill, S.L. Walmsley, E. Toma, B. Conway, I.W. Fong, A.R. Rachlis, K.E. Williams, G.E. Garber, W.F. Schlech.

    • Final approval of the article: S.D. Shafran, L.D. Mashinter, P. Phillips, R.G. Lalonde, M.J. Gill, S.L. Walmsley, E. Toma, B. Conway, I.W. Fong, A.R. Rachlis, G.E. Garber, W.F. Schlech, F. Smaill.

    • Provision of study materials or patients: S.D. Shafran, P. Phillips, S.L. Walmsley, E. Toma, B. Conway, I.W. Fong, A.R. Rachlis, K.E. Williams, G.E. Garber, W.F. Schlech, F. Smaill.

    • Statistical expertise: S.D. Shafran.

    • Obtaining of funding: S.D. Shafran.

    • Administrative, technical, or logistic support: S.D. Shafran, L.D. Mashinter, M.J. Gill, B. Conway.

    • Collection and assembly of data: S.D. Shafran, L.D. Mashinter, P. Phillips, R.G. Lalonde, M.J. Gill, S.L. Walmsley, E. Toma, B. Conway, I.W. Fong, A.R. Rachlis, W.F. Schlech.

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