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

5 November 2002 | Volume 137 Issue 9 | Pages 734-737

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 x 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 x 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 x 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.

Editors' Notes Context The 1999 U.S. Public Health Service/Infectious Diseases Society of America recommendations suggest that prophylaxis against Mycobacterium avium complex infection can be discontinued after a favorable response to highly active antiretroviral therapy (HAART) in HIV-infected patients but that antimycobacterial therapy be continued for life in patients who have had active infection. Contribution In this retrospective study of 52 HIV-infected adults whose active M. avium complex infections were controlled after a favorable response to HAART and whose antimycobacterial therapy was stopped, only 1 patient had developed recurrent M. avium complex disease 37 months after stopping antimycobacterial therapy and 2 months after stopping HAART. Implications Stopping antimycobacterial therapy in patients previously infected with M. avium complex disease who favorably responded to HAART seems safe and can simplify drug regimens, improve adherence, and decrease treatment costs. –The Editors

 

Author and Article Information

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.

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. [Abstract/Free Full Text]).

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.