Withdrawal of Antifungal Treatment for Histoplasmosis in Patients After Improved Immune Response to Anti-HIV Drugs

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00006316
First received: September 28, 2000
Last updated: July 30, 2008
Last verified: February 2004
  Purpose

The purpose of this study is to determine whether stopping preventive histoplasmosis medications in patients who are currently receiving effective anti-HIV drugs will place them at risk for getting histoplasmosis again.

Histoplasmosis is a serious opportunistic (AIDS-related) infection that responds well to antifungal medications. Before anti-HIV drugs, patients with histoplasmosis required lifelong antifungal therapy. Patients who take anti-HIV drugs for a long time may see an improvement in their immune system functions. Improved immune function may eliminate the need for long-term preventive treatment with antifungal agents. Doctors want to see if the improved immune functions allow preventive treatment for histoplasmosis to be stopped. (This study has been changed to include histoplasmosis treatment with drugs other than itraconazole.)


Condition
HIV Infections
Histoplasmosis

Study Type: Observational
Official Title: Discontinuation of Antifungal Therapy for Histoplasmosis Following Immunologic Response to Antiretroviral Therapy

Resource links provided by NLM:


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

Estimated Enrollment: 50
Detailed Description:

Histoplasmosis is a serious opportunistic infection in persons with AIDS that demonstrates an excellent response to antifungal therapy. However, until the advent of highly active antiretroviral therapy (HAART), patients with histoplasmosis required lifelong suppressive antifungal therapy. It is thought that immune reconstitution as a result of HAART may diminish the need for chronic therapy. Histoplasmosis offers an opportunity to examine the concept of discontinuation of maintenance therapy as it is rapidly diagnosed and effectively treated with itraconazole [AS PER AMENDMENT 9/27/00: or other appropriate therapy for disseminated histoplasmosis] should relapse occur.

Patients discontinue antifungal maintenance therapy. Patients are seen for routine visits every 8 weeks and urine and serum specimens are collected for real time Histoplasma antigen testing and immunologic parameters. Patients with suspected recurrence, as determined by clinical or routine laboratory findings consistent with recurrent histoplasmosis, are reevaluated within 1 week of onset of these findings. Patients with suspected recurrence based on a serum or urine Histoplasma antigen rise of 2 units or more, in the absence of clinical or routine laboratory findings consistent with histoplasmosis, are reevaluated within 2 weeks. All patients with suspected recurrence have more frequent evaluations and additional laboratory tests. Those with negative studies resume bimonthly follow-up. All patients who develop proven (positive culture or positive fungal stain of tissues or body fluids) or probable relapse (clinical findings of relapse with an increase in antigen of 4.1 units or more, or no clinical findings but increases in antigen levels on repeated testing with the most recent antigen test demonstrating an increase in antigen of 4.1 units or more) or who experience persistent reduction of CD4 cell count to below 100/mm3 have antifungal induction therapy reinstituted. Patients remain on study for at least 12 months with regular follow-up/evaluations.

  Eligibility

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

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are 13 years or older.
  • Have consent of parent or guardian if under 18 years of age.
  • Have HIV infection.
  • Have 2 CD4 cell counts above 150 cells/mm3 (1 of which has been obtained within 6 months and the other within 30 days before entry). Note: The 2 CD4 counts used for eligibility must be from tests performed at least 1 week apart.
  • Have received at least 1 year of treatment for histoplasmosis. (This study has been changed to include patients who have received histoplasmosis treatment with drugs other than itraconazole.)
  • Are receiving treatment for histoplasmosis or have stopped treatment within 24 weeks of study entry.
  • Have had histoplasmosis before but are free of any signs of histoplasmosis at entry into the study.
  • Have a negative pregnancy test within 14 days of study entry.
  • Have been on anti-HIV drugs for at least 24 successive weeks and have been on a stable anti-HIV drug combination for at least 8 weeks before entry.

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Have any recurrence of histoplasmosis within 4 weeks of study entry.
  • Have received medications that affect the immune system including chemotherapy or corticosteroids within the last 2 months. (This study has been changed. Patients taking IL-2 are no longer excluded.)
  • Have a systemic infection. Patients on stable preventive treatment for certain opportunistic (AIDS-related) infections for at least 3 months will be eligible.
  • Require treatment for fungal infections with systemic antifungal medications.
  • Have meningitis or brain or spinal cord damage thought to be caused by Histoplasma infection.
  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: NCT00006316

Locations
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
University of California San Francisco
San Francisco, California, United States, 941104206
United States, Georgia
Emory Univ
Atlanta, Georgia, United States, 30308
United States, Illinois
Cook County Hosp
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
Wishard Hosp
Indianapolis, Indiana, United States, 46202
United States, Nebraska
Univ of Nebraska Med Ctr
Omaha, Nebraska, United States, 681985130
United States, New York
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Texas
Univ of Texas, Southwestern Med Ctr of Dallas
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Investigators
Study Chair: Mitch Goldman
Study Chair: Judy Aberg
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00006316     History of Changes
Other Study ID Numbers: ACTG A5038, AACTG A5038
Study First Received: September 28, 2000
Last Updated: July 30, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Histoplasmosis
Antifungal Agents
Recurrence
Anti-HIV Agents

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Histoplasmosis
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Mycoses
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Antifungal Agents
Miconazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014