Cryptococcal Meningitis, HIV Infections
Conditions
Keywords
HIV-1, Africa, Botswana, Highly active antiretroviral therapy, treatment naive
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.
Interventions
OTHEREarly 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.
Sponsors
Doris Duke Charitable Foundation
University of Pennsylvania
Botswana-UPenn Partnership
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in the CSF CFUs between the immediate and standard ART initiation groups | 4 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Botswana
Outcome results
None listed