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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00976040
Recruitment Status : Completed
First Posted : September 14, 2009
Last Update Posted : February 7, 2012
Doris Duke Charitable Foundation
University of Pennsylvania
Information provided by (Responsible Party):
Gregory Bisson, Botswana-UPenn Partnership

Brief Summary:

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 or disease Intervention/treatment Phase
Cryptococcal Meningitis HIV Infections Other: Early antiretroviral therapy Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : September 2009
Actual Primary Completion Date : November 2011
Actual Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Meningitis

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Change in the CSF CFUs between the immediate and standard ART initiation groups [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. Grade 3 or 4 adverse events [ Time Frame: 6 months ]
    each participant is followed up for 6 months after the initiation of HAART

  2. Clearance of C. neoformans antigen from CSF and blood. [ Time Frame: 6 months ]
  3. Change in the number of peripheral blood mononuclear cells responding to C. neoformans [ Time Frame: 4 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT00976040

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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
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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
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Gregory Bisson, Assistant Professor of Medicine, Botswana-UPenn Partnership Identifier: NCT00976040    
Other Study ID Numbers: THE BOTSHELO STUDY
First Posted: September 14, 2009    Key Record Dates
Last Update Posted: February 7, 2012
Last Verified: February 2012
Keywords provided by Gregory Bisson, Botswana-UPenn Partnership:
Highly active antiretroviral therapy
treatment naive
Additional relevant MeSH terms:
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Meningitis, Cryptococcal
Meningitis, Fungal
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Fungal Infections
Central Nervous System Infections
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents