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

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ClinicalTrials.gov Identifier: NCT00006316
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : August 1, 2008
Information provided by:

Study Description
Brief Summary:

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 or disease
HIV Infections Histoplasmosis

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.

Study Design

Study Type : Observational
Estimated Enrollment : 50 participants
Official Title: Discontinuation of Antifungal Therapy for Histoplasmosis Following Immunologic Response to Antiretroviral Therapy

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006316

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
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Mitch Goldman
Study Chair: Judy Aberg
More Information

ClinicalTrials.gov Identifier: NCT00006316     History of Changes
Other Study ID Numbers: ACTG A5038
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: August 1, 2008
Last Verified: February 2004

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

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP3A Inhibitors