A Study to Examine the Effects of Stopping Preventive Therapy for Disseminated Mycobacterium Avium Complex (DMAC) in HIV-Positive Patients

This study is currently recruiting patients.

Sponsored by

National Institute of Allergy and Infectious Diseases (NIAID)

bulletPurpose

The purpose of this study is to evaluate the effects of stopping preventive therapy for DMAC in HIV-positive patients who (1) have been treated for DMAC for at least 12 months and are now free of any signs of DMAC for at least 16 weeks, and (2) have improved immune systems (CD4 cell counts greater than or equal to 100 cells/mm3) due to anti-HIV drug therapy. DMAC is a serious and sometimes life-threatening infection that usually only affects HIV-positive patients with CD4 cell counts (cells of the immune system that fight infection) less than 50 cells/mm3. It is recommended that people who are likely to get DMAC be placed on preventive medications which help reduce the risk of infection. New anti-HIV combination drug therapies can increase CD4 cell counts and can reduce the level of HIV in the blood. When CD4 counts are increased, risk of DMAC infection is less. This study examines whether it is possible to stop preventive therapy for DMAC when CD4 counts are high without placing individuals at risk for getting DMAC again. You will take your DMAC preventive medications for 6 weeks. After 6 weeks, you will stop taking these medications, but you will be monitored for the rest of the study (up to 110 weeks). You will have physical exams, blood tests, and give urine samples at the beginning of the study, and then at Weeks 6, 10, 14, and then every 8 weeks after until the end of the study. At study entry, you will also have a bone marrow biopsy done (the doctor will remove a small amount of bone marrow from your hip bone with a needle after numbing the area). You will also have several skin tests done during the study to test your immune system. You must stay on your anti-HIV drugs throughout the study. You may be eligible for this study if you: Are HIV-positive. Have a CD4 cell count greater than or equal to 100 cells/mm3 within 60 days and within 14 days prior to entry. Have been treated for DMAC with a drug regimen including at least 2 antimycobacterial drugs for at least 12 months, and have been free of symptoms for at least 16 weeks prior to study entry. Have been on anti-HIV therapy for at least 16 weeks and have been on stable anti-HIV therapy for at least 8 weeks prior to study entry. Are at least 13 years old (need consent if under 18). You will not be eligible for this study if you: Have any active infection (unless you have been on stable chronic suppressive therapy for at least 3 months). Are pregnant.

Condition

HIV Infections

Mycobacterium avium-intracellulare Infection

Study Type and Design: Prevention, Monitoring; Multicenter Study

Official Title: A Study of Discontinuing Maintenance Therapy in Subjects with Disseminated Mycobacterium Avium Complex (DMAC)

Further Study Details: To determine if anti-mycobacterial therapy can be withdrawn from patients who meet the following conditions: prior treatment with macrolide-based therapy over 12 months; asymptomatic for Mycobacterium avium complex (MAC) for at least 16 weeks; CD4+ counts of at least 100 cells/mm3; receipt of antiretroviral therapy for 16 weeks. To estimate the duration of time patients remain free of MAC infection.  A growing body of evidence suggests AIDS-related morbidity and mortality significantly decrease where potent antiretroviral therapies are used. HAART (highly active antiretroviral therapy) seems to significantly reduce the incidence of MAC. This study tests the validity of those observations.  Peripheral blood cultures and bone marrow (aspirate) samples from 50 eligible patients previously diagnosed with disseminated Mycobacterium avium complex (DMAC) are assessed for microbiologic sterilization of MAC at the time of study entry. If either bone marrow or blood cultures test positive for MAC, patients are discontinued from study. If cultures prove sterile, patients receive 6 weeks of treatment and then discontinue MAC therapy at Week 6 (entry into Step 2 of study). They are then monitored for clinical signs and symptoms of MAC recurrence and for the presence of mycobacteria in blood cultures. In cases of increased viral load during study, modification of antiretroviral therapy is allowed at the discretion of the patient's provider.  

bulletEligibility

Ages Eligible for Study:  13 Years  and above Inclusion Criteria

Patients must have: 1. Documented HIV infection prior to study entry by presence of antibody (ELISA with Western blot confirmation), serum p24 antigen, recovery of HIV in culture, HIV RNA PCR or a diagnosis of AIDS based on 1993 CDC criteria. 2. One CD4+ cell count of at least 100 cells/mm3 within 30 days [AS PER AMENDMENT 3/15/99: 60 days] prior to study entry performed at any laboratory and one CD4+ cell count of at least 100 cells/mm3 within 14 days prior to study entry performed at an ACTG-certified laboratory. [AS PER AMENDMENT 3/15/99: CD4+ cell counts must be done at least 24 hours apart.] 3. Any previous diagnosis of DMAC by either bone marrow or peripheral blood culture. 4. Absence of unexplained clinical signs or symptoms of MAC disease (e.g., fever greater than 30 degrees Celsius for at least 2 days; night sweats for at least 2 days; weight loss of greater than 5% body weight; diarrhea with greater than 3 unformed stools/day for at least 2 days; hepatomegaly [clinically assessed by exam]; splenomegaly [clinically assessed by exam]; elevation of alkaline phosphatase of at least 2 times the upper limit of normal; or severe anemia [Hct less than 25]) for 16 weeks prior to study entry.

Required: 1. Treatment with antiretroviral therapy for at least 16 weeks and a stable antiretroviral regimen for at least 8 weeks prior to study entry. 2. Treatment with a minimum of a 2-drug antimycobacterial regimen for at least 12 months (i.e., clarithromycin or azithromycin plus either ethambutol or rifabutin).

Not pregnant

CD4 Unspecified.

Platelet Count >= 20000 /mm3 Within 14 days of study entry.

Exclusion Criteria

Patients with the following symptoms or conditions are excluded: Any active systemic infection. (Note: Patients on stable chronic suppressive therapy, such as CMV, cryptococcois, or histoplasmosis, for at least 3 months are eligible.)

Excluded: Systemic corticosteroids, immunomodulators, cytotoxic chemotherapy, vaccines, IVIG, or GM-CSF within 2 months of study entry. (Note: G-CSF is allowed.)

Excluded: Continued therapy with azithromycin, clarithromycin, ethambutol, rifamycins, or fluoroquinolones for the management of disease other than MAC.

Excluded: Prisoners.

bulletLocation and Contact Information

California

Univ of California / San Diego Treatment Ctr, 2760 5th Ave / Suite 300   San Diego,   California,    92103-6325,   United States; Recruiting

Jill Kunkel       619-543-8080    jkunkel@ucsd.edu 

California

San Francisco Gen Hosp, 995 Potrero Ave / Building 80 / Ward 84   San Francisco,   California,    94110-2859,   United States; Recruiting

Marc Gould       415-476-9296    mgould@sfaids.ucsf.edu 

California

San Francisco AIDS Clinic / San Francisco Gen Hosp, 995 Potrero Ave / Building 80 / Ward 84   San Francisco,    California,   94110-2859,   United States; No longer recruiting

Marc Gould       415-476-9296    mgould@sfaids.ucsf.edu 

California

Stanford Univ Med Ctr, 300 Pasteur Dr / S-156   Stanford,   California,   94305-5107,    United States; Recruiting

Debbie Slamowitz       415-723-2804    dslam@leland.stanford.edu 

California

Univ of Southern California / LA County USC Med Ctr, 2020 Zonal Ave / Room 309   Los Angeles,   California,    90033-1079,   United States; Recruiting

Luis Mendez     1300 North Mission Road   Los Angeles,    323-343-8288     lmendez@phad.hsc.usc.edu  

California

San Mateo AIDS Program / AIDS Community Rsch Consortium, 3700 Edison St   San Mateo,   California,    94403-4462,   United States; Recruiting

Debbie Slamowitz      Room S-156   Stanford,    650-723-2804     dslam@leland.stanford.edu  

California

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium, 751 South Bascom Ave   San Jose,   California,    95128-2699,   United States; Recruiting

Debbie Slamowitz      Room S-156   Stanford,    650-723-2804     dslam@leland.stanford.edu  

California

Willow Clinic, 705 Willow Rd    Menlo Park,   California,   94205,   United States; Recruiting

Debbie Slamowitz     300 Pasteur Dr, Room S-156   Stanford,    650-723-2804     dslam@leland.stanford.edu  

Colorado

Univ of Colorado Health Sciences Ctr, 4200 East 9th Ave / Colorado ACTU / Campus Box B-163   Denver,    Colorado,   80262,   United States; Recruiting

M Graham Ray       303-372-5535    graham.ray@uchsc.edu 

Florida

Univ of Miami School of Medicine, 1800 Northwest 10th Ave / P O Box 016960   Miami,   Florida,    33136-1013,   United States; No longer recruiting

Leslie Thompson       305-243-3841    thomps04@pop.fstrf.org 

Georgia

Emory Univ, 341 Ponce de Leon Ave    Atlanta,   Georgia,   30329,   United States; Recruiting

Beth Dean       404-616-0654    tbdean@emory.edu 

Hawaii

Univ of Hawaii, 3675 Kilauea Ave / Leahi Hosp   Young Building 6th Floor   Honolulu,   Hawaii,    96816,   United States; Recruiting

Debra M Ogata-Arakaki      Young Bldg, Sixth Floor   Honolulu,     808-737-2751    ogataara@hawaii.edu  

Illinois

Rush Presbyterian - Saint Luke's Med Ctr, 600 South Paulina St / Suite 143-AAF   Chicago,   Illinois,    60612,   United States; Recruiting

Jan Fritsche       312-942-4810    smartin5@rush.edu 

Indiana

Indiana Univ Hosp, 550 North Univ Blvd / Room 0674   Indianapolis,   Indiana,   46202-5250,    United States; Recruiting

Beth Zwickl       317-274-8456    Bwzwickl@iupui.edu 

Indiana

Wishard Hosp / Indiana Univ Hosp, 1001 West 10th St / OPW 430   Indianapolis,   Indiana,   46202,    United States; Recruiting

Beth Zwickl     550 North Univeristy Boulevard   Indianapolis,    317-274-8456     bwzwickl@iupui.edu 

Maryland

Johns Hopkins Hosp, 1830 East Monument St / Room 8074   Baltimore,   Maryland,   21205-2196,    United States; Recruiting

Rebecca Becker       410-955-4370    Becker.Becy@FSTRF.org 

New York

Bellevue Hosp / New York Univ Med Ctr, 550 First Ave / ACTU C&D Bldg / Old Bellevue   New York,    New York,   10016,   United States; Recruiting

Maura Laverty       212-263-6565    laverty.maura@fstrf.org 

New York

Mount Sinai Med Ctr, One Gustave Levy Place / PO Box 1042   New York,   New York,   10029,    United States; Recruiting

Eileen Chusid       212-241-0433    CHUSID.EILEEN@FSTRF.ORG 

New York

Beth Israel Med Ctr, First Ave at 16th St / 19 Baird Hall   New York,   New York,   10003,    United States; Recruiting

Ann Marshak       212-420-4432    marshak.ann@fstrf.org 

New York

SUNY / Erie County Med Ctr at Buffalo, 462 Grider St / Suite 35   Buffalo,   New York,    14215,   United States; Recruiting

Brenda Stamos       716-898-3158    bjstamos@acsu.buffalo.edu 

North Carolina

Univ of North Carolina, 516 Burnett - Womack Bldg / CB #7215   Chapel Hill,   North Carolina,    27599-7215,   United States; Recruiting

Barbara Longmire       919-966-7883    LONGBAR@MED.UNC.EDU 

Ohio

Univ of Cincinnati, Eden and Bethesda Ave   Cincinnati,   Ohio,   45267-0405,   United States; No longer recruiting

Tammy Powell       513-584-8373    powelltm@email.uc.edu 

Pennsylvania

Univ of Pennsylvania at Philadelphia, 549 Johnson Pavilion / 36th and Hamilton Walk   Philadelphia,    Pennsylvania,   19104-6073,   United States; Recruiting

Christopher Helker      536 Johnson Pavilion   Philadelphia,     215-349-8092    chelker2@mail.med.upenn.edu 

Study chairs or principal investigators

Judith Aberg,  Study Chair

Judith Currier,  Co-Chair

bulletMore Information

Study ID Numbers  ACTG 393

NLM Identifier  NCT00000907

Recruitment status verified  May 31, 2000

 

Last Updated  April 5, 1999

Back