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The Effects of Treatment for Mycobacterium Avium Complex (MAC) on the Cells of HIV-Infected Patients

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000860
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: July 1999
  Purpose

To determine if treatment of MAC infection in HIV-1 infected persons is associated with the decreases in plasma levels of TNF-alpha.

Infection with MAC is a poor prognostic indicator in persons with AIDS. Evidence suggests that this poor outcome is not simply a reflection of greater immune impairment in AIDS patients with MAC infection, but rather may be a direct or indirect consequence of infection with mycobacterium. Survival of AIDS patients with MAC is shorter than those without MAC. Studies show that treatment for MAC improves the survival of MAC infected patients to nearly the survival of AIDS patients without MAC. Treatment of MAC with clarithromycin containing regimens is associated with decreased symptoms and prolonged survival. There is evidence, however, that mycobacterial infection may enhance propagation of the human immunodeficiency virus through mechanisms that may involve enhanced expression of pro inflammatory cytokines. It is unclear to what extent cytokine abnormalities contribute to this symptom complex and to what extent treatment of MAC infection will reverse these cytokine abnormalities.


Condition
Mycobacterium Avium-Intracellulare Infection
HIV Infections

Study Type: Observational
Study Design: Observational Model: Natural History
Official Title: Effects of Treatment for MAC Infection on Cytokine Expression in HIV-Infected Persons.

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 24
Detailed Description:

Infection with MAC is a poor prognostic indicator in persons with AIDS. Evidence suggests that this poor outcome is not simply a reflection of greater immune impairment in AIDS patients with MAC infection, but rather may be a direct or indirect consequence of infection with mycobacterium. Survival of AIDS patients with MAC is shorter than those without MAC. Studies show that treatment for MAC improves the survival of MAC infected patients to nearly the survival of AIDS patients without MAC. Treatment of MAC with clarithromycin containing regimens is associated with decreased symptoms and prolonged survival. There is evidence, however, that mycobacterial infection may enhance propagation of the human immunodeficiency virus through mechanisms that may involve enhanced expression of pro inflammatory cytokines. It is unclear to what extent cytokine abnormalities contribute to this symptom complex and to what extent treatment of MAC infection will reverse these cytokine abnormalities.

All patients diagnosed with MAC and who will initiate at least a 2 drug clarithromycin containing MAC treatment regimen will be eligible for participation. Blood and urine will be obtained from each patient at the following timepoints: Pre-Entry (within 7 days prior to study entry), week 4, and week 8. Sites will process and ship specific samples to Case Western Reserve University (CWRU). Various assays and analyses will be performed by CWRU. NOTE: Patients will receive no treatment on this study, however, all patients must be receiving at least a 2 drug clarithromycin containing treatment regimen for MAC either as part of participation in other studies or as prescribed by the subject's health care provider.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Patients should have successfully completed therapy or be on stable therapy for any acute infectious processes other than MAC prior to study entry.

Patients must have:

  • Documented HIV infection.
  • Either symptomatic MAC disease as defined by a history of clinical signs and symptoms, plus one blood culture positive for MAC or AFB obtained within the previous 90 days, OR asymptomatic MAC disease as defined by 2 blood cultures positive for MAC or AFB obtained within 90 days of entry.
  • Signed parental consent for patients less than 18 years of age.

Prior Medication:

Allowed:

  • Patients who have received presumptive or empiric antimycobacterial therapy prior to study entry may be enrolled if they have been treated for no more than 72 hours prior to study entry.
  • Patients who have been receiving prophylaxis with azithromycin, clarithromycin and/or rifabutin may be enrolled.
  • Patients should have successfully completed therapy or be on stable therapy for any acute infectious processes other than MAC prior to study entry.

Required:

  • Patients must be on a stable antiretroviral regimen (same drug or combination drugs; dose modifications allowed) for at least 4 weeks prior to study entry.

NOTE:

  • Patients will be requested NOT to modify or add new drugs to their stable ARV regimen for the duration of this study. Patients who absolutely require ARV changes at any time prior to week 8 will continue on study, however, their data will be analyzed separately.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Previous enrollment and permanent study drug discontinuation in ACTG 223.

Note:

  • Co-enrollment in ACTG 223 and ACTG 853 is acceptable, however enrollment in both studies must be simultaneous.
  • This protocol does not meet federal requirements governing prisoner participation in clinical trials and should not be considered by local IRBs for the recruitment of prisoners.

Concurrent Medication:

Excluded:

  • Cytokine inhibitors.
  • Corticosteroids.
  • Thalidomide.
  • Pentoxifylline or any other immunomodulator.
  • Any interleukin.
  • Colony stimulating factors (G-CSF or GM-CSF)

Patients with the following prior conditions will be excluded:

  • Subjects who have had an opportunistic infection (other than MAC) within 14 days immediately preceding study entry.

Prior Medication:

Excluded within the 14 days immediately preceding study entry:

  • Cytokine inhibitors.
  • Corticosteroids.
  • Thalidomide.
  • Pentoxifylline or any other immunomodulator.
  • Any interleukin.
  • Colony stimulating factors (G-CSF or GM-CSF)

Prior Treatment:

Excluded:

  • Patients who have received a blood transfusion within the 14 days immediately preceding study entry.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000860

Locations
United States, California
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, District of Columbia
Washington Reg AIDS Prog / Dept of Infect Dis
Washington, District of Columbia, United States, 20422
United States, Illinois
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
United States, Indiana
Division of Inf Diseases/ Indiana Univ Hosp
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Investigators
Study Chair: MacArthur R
Study Chair: Benson C
Study Chair: Lederman M
  More Information

Publications:
Benson CA. MAC: pathogenesis and treatment. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:166
MacArthur RD, Lederman M, Benson CA, Chernoff MC, Mahon LF, Yen-Lieberman B, Purvis S. ACTG 853: effects of treatment for MAC infection on cytokine expression in HIV-infected persons. Int Conf AIDS. 1998;12:1050 (abstract no 60279)
MacArthur RD, Lederman M, Benson CA, Chernoff MC, Mahon LF, Yen-Lieberman B, Purvis S, MacGregor RR. ACTG 853: effects of treatment for MAC infection on cytokine expression in HIV-infected persons. Intersci Conf Antimicrob Agents Chemother. 1998 Sep 24-27;38:403 (abstract no I-130)

ClinicalTrials.gov Identifier: NCT00000860     History of Changes
Other Study ID Numbers: ACTG 853
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Tumor Necrosis Factor
AIDS-Related Opportunistic Infections
Mycobacterium avium-intracellulare Infection
Drug Therapy, Combination
Anti-HIV Agents

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Communicable Diseases
HIV Infections
Infection
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Mycobacterium Infections, Nontuberculous
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 24, 2014