Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis

This study has been completed.
Sponsor:
Collaborators:
Doris Duke Charitable Foundation
University of Pennsylvania
Information provided by (Responsible Party):
Gregory Bisson, Botswana-UPenn Partnership
ClinicalTrials.gov Identifier:
NCT00976040
First received: September 11, 2009
Last updated: February 3, 2012
Last verified: February 2012
  Purpose

The goal of this randomized clinical trial is to compare early versus standard timing of initiation of antiretroviral therapy (ART) with respect to clearance of Cryptococcus neoformans from cerebrospinal fluid (CSF) among HIV-infected adults with Cryptococcal Meningitis.

The investigators hypothesize that early ART mediates more rapid clearance of C. neoformans from CSF, as manifested by a greater rate of decrease in C. neoformans colony forming units (CFUs) during the first 28 days after initiating antifungal treatment.

Secondary hypotheses are that recovery of pathogen specific cellular immunity directed at C. neoformans, as manifested by increases in the number and function of C. neoformans-specific peripheral blood mononuclear cells is associated with 1) ART and 2) pathogen clearance. In addition, patients randomized to the intervention arm will have more rapid clearance of antigen levels in CSF and serum and will have a lower incidence of grade 3 and 4 Adverse events.


Condition Intervention Phase
Cryptococcal Meningitis
HIV Infections
Other: Early antiretroviral therapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis

Resource links provided by NLM:


Further study details as provided by Botswana-UPenn Partnership:

Primary Outcome Measures:
  • Change in the CSF CFUs between the immediate and standard ART initiation groups [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Grade 3 or 4 adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    each participant is followed up for 6 months after the initiation of HAART

  • Clearance of C. neoformans antigen from CSF and blood. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in the number of peripheral blood mononuclear cells responding to C. neoformans [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: September 2009
Study Completion Date: December 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Early antiretroviral therapy
Subjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment.
Other: Early antiretroviral therapy

The intervention is early initiation of antiretroviral therapy after diagnosis of Cryptococcal meningitis.

In the intervention/experimental arm, triple-drug highly active antiretroviral therapy regimens will be initiated within 7 days of diagnosis of Cryptococcal meningitis.

No Intervention: Standard antiretroviral therapy
Subjects randomized to this arm will initiate antiretroviral therapy approximately 4 weeks after enrollment.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV 1 infection confirmed by licensed ELISA kit and/or detectable Viral load.
  • Confirmed Cryptococcal meningitis on the current admission by India ink or CSF cryptococcal antigen
  • ART naive at the time of enrollment
  • 21 years old and above
  • Ability and willingness to give written informed consent to participate in the study
  • Able (as assessed by the patient's medical team)to initiate amphotericin B for cryptococcal meningitis
  • Initiated amphotericin B 72 hours or less prior to assessment for enrollment or not on amphotericin B at the time of assessment for enrollment
  • Agrees to obtain outpatient care after discharge within 50 kilometers from Princess Marina Hospital,Scottish Livingstone Hospital and Bamalete Lutheran Hospital

Exclusion Criteria:

  • Recent (within the past 4 weeks) antifungal use
  • Pregnant or breastfeeding
  • Initiated anti-tubercular therapy 2 weeks or less prior to assessment for enrollment.
  • Bacterial meningitis at the time of assessment for enrollment.
  • Recent (within the past 1 month) use of the following:systemic cancer chemotherapy,oral or intravenous corticosteroids or other immunomodulators.
  • Judged by study coordinator to be likely to initiate chemotherapy or any other immunomodulatory therapy prior to the 4 week LP.
  • Imprisoned.
  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: NCT00976040

Locations
Botswana
Princess Marina Hospital,Bamalete Lutheran Hospital and Scottish Livingstone Hospital
Gaborone,Ramotswa,Molepolole, Botswana
Sponsors and Collaborators
Botswana-UPenn Partnership
Doris Duke Charitable Foundation
University of Pennsylvania
Investigators
Principal Investigator: Gregory P Bisson, MD,MSCE Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Principal Investigator: Pablo Tebas, MD Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
  More Information

No publications provided by Botswana-UPenn Partnership

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gregory Bisson, Assistant Professor of Medicine, Botswana-UPenn Partnership
ClinicalTrials.gov Identifier: NCT00976040     History of Changes
Other Study ID Numbers: THE BOTSHELO STUDY
Study First Received: September 11, 2009
Last Updated: February 3, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Botswana-UPenn Partnership:
HIV-1
Africa
Botswana
Highly active antiretroviral therapy
treatment naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Meningitis
Meningitis, Cryptococcal
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Fungal
Central Nervous System Fungal Infections
Mycoses
Cryptococcosis

ClinicalTrials.gov processed this record on September 15, 2014