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