Clinical Trials


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

This study has been completed
Botswana-UPenn Partnership

Doris Duke Charitable Foundation
University of Pennsylvania

Information provided by (Responsible Party)
Gregory Bisson, Botswana-UPenn Partnership Identifier

First received: September 11, 2009
Last updated: February 3, 2012
Last Verified: February 2012
History of Changes


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
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

Further study details as provided by Gregory Bisson, Botswana-UPenn Partnership:

Primary Outcome Measures

  • Change in the CSF CFUs between the immediate and standard ART initiation groups [ Time Frame: 4 weeks ]
Secondary Outcome Measures:
  • Grade 3 or 4 adverse events [ Time Frame: 6 months ]
    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 ]
  • Change in the number of peripheral blood mononuclear cells responding to C. neoformans [ Time Frame: 4 weeks ]

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.


Ages Eligible for Study: 21 Years to 80 Years  
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.

contacts and locations

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 identifier: NCT00976040


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


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

More Information

Responsible Party: Gregory Bisson, Assistant Professor of Medicine, Botswana-UPenn Partnership Identifier: NCT00976040   History of Changes  
Other Study ID Numbers: THE BOTSHELO STUDY  
Study First Received: September 11, 2009  
Last Updated: February 3, 2012  

Keywords provided by Gregory Bisson, Botswana-UPenn Partnership:

Highly active antiretroviral therapy
treatment naive

Additional relevant MeSH terms:
Meningitis, Cryptococcal
Anti-Retroviral Agents processed this data on May 24, 2020
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