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

HIV Infections Clinical Trial

— Crypto  

Official title:

A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00976040
• Other study ID #: THE BOTSHELO STUDY
• Status: Completed
• Phase: Phase 4
• First received: September 11, 2009
• Last updated: February 3, 2012
• Start date: September 2009
• Est. completion date: December 2011

Study information

• Verified date: February 2012
• Source: Botswana-UPenn Partnership
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cryptococcal Meningitis
• HIV Infections
• Meningitis
• Meningitis, Cryptococcal

Intervention

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.

Locations

Country	Name	City	State
Botswana	Princess Marina Hospital,Bamalete Lutheran Hospital and Scottish Livingstone Hospital	Gaborone,Ramotswa,Molepolole

Sponsors (3)

Lead Sponsor	Collaborator
Botswana-UPenn Partnership	Doris Duke Charitable Foundation, University of Pennsylvania

Country where clinical trial is conducted

Botswana, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the CSF CFUs between the immediate and standard ART initiation groups		4 weeks	No
Secondary	Grade 3 or 4 adverse events	each participant is followed up for 6 months after the initiation of HAART	6 months	Yes
Secondary	Clearance of C. neoformans antigen from CSF and blood.		6 months	No
Secondary	Change in the number of peripheral blood mononuclear cells responding to C. neoformans		4 weeks	No