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

Phase 4

Completed

• Conditions: Cryptococcal Meningitis; HIV Infections
• Interventions: Other: Early antiretroviral therapy

• Registration Number: NCT00976040
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-11
• Study First Submitted QC: 2009-09-11
• Study First Posted: 2009-09-14
• Primary Completion: 2011-11
• Study Completion: 2011-12
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-03
• Last Update Posted: 2012-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early antiretroviral therapy	Early antiretroviral therapy	Subjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment.

Primary Outcome Measures

Name	Time	Method
Change in the CSF CFUs between the immediate and standard ART initiation groups	4 weeks

Secondary Outcome Measures

Name	Time	Method
Grade 3 or 4 adverse events	6 months	each participant is followed up for 6 months after the initiation of HAART
Clearance of C. neoformans antigen from CSF and blood.	6 months
Change in the number of peripheral blood mononuclear cells responding to C. neoformans	4 weeks

Trial Locations

Locations (1)

Princess Marina Hospital,Bamalete Lutheran Hospital and Scottish Livingstone Hospital; 🇧🇼 Gaborone,Ramotswa,Molepolole, Botswana