Optimal Time to Start Antiretroviral Therapy in HIV-infected Adults With Cryptococcal Meningitis (Crypto)
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.
|Cryptococcal Meningitis HIV Infections||Other: Early antiretroviral therapy||Phase 4|
|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|
- Change in the CSF CFUs between the immediate and standard ART initiation groups [ Time Frame: 4 weeks ]
- 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 ]
|Study Start Date:||September 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00976040
|Princess Marina Hospital,Bamalete Lutheran Hospital and Scottish Livingstone Hospital|
|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|