The Cryptococcal Optimal ART Timing (COAT) trial seeks to determine after cryptococcal meningitis (CM) whether early initiation of antiretroviral therapy (ART) prior to hospital discharge results in superior survival compared to standard initiation of ART started as an outpatient.
After 7-11 days of amphotericin B therapy, subjects will be randomized in a 1:1 allocation to: * Early initiation of ART (Experimental Group) = ART initiated within 48 hours after study entry, OR * Standard initiation of ART (Control Group) = ART at \>=4 weeks after study entry HIV therapy will be with efavirenz plus nucleoside backbone per national guidelines for first line therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
177
Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.
Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.
GF Jooste Hospital
Cape Town, South Africa
Infectious Disease Institute, Mulago Hospital, Makerere University
Kampala, Uganda
Mbarara University of Science and Technology
Mbarara, Uganda
Mortality
Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.
Time frame: 26 weeks from study entry
Incidence of Immune Reconstitution Inflammatory Syndrome
Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.
Time frame: 46 weeks
Incidence of Cryptococcal-relapse
Incidence of culture positive cryptococcal meningitis relapse
Time frame: 46 weeks
Safety of ART Initiation
Incidence of Adverse Events (Grade 3,4,5) through 46-weeks, as defined by the National Institute of Allergy and Infectious Diseases, Division of AIDS toxicity classification scale, version 2009.
Time frame: 46 weeks
46-week Survival
46-week survival by time-to-event analysis of all subjects enrolled
Time frame: 46 weeks
HIV-1 Viral Suppression
HIV-1 virologic suppression to \<400 copies/mL at 26-weeks after enrollment
Time frame: 26 weeks
Antiretroviral Therapy Tolerability
Incidence of antiretroviral therapy interruption by \>=3 consecutive days
Time frame: 26 weeks
Karnofsky Functional Status
Functional status via Karnofsky performance status score at 4, 26, 46 weeks. Karnofsky Scale: 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
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Time frame: 46 weeks
Microbiologic Clearance
Microbiologic clearance of cryptococcus as measured by serial quantitative cryptococcal cultures collected at diagnosis through 14 days of amphotericin therapy. The early fungicidal activity (EFA) of the rate of clearance is expressed as log10 colony forming units (CFU) of Cryptococcus neoformans per mL of CSF per day.
Time frame: 4 weeks