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NCT Number: NCT00976040

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.

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Key information

Conditions

Cryptococcal Meningitis Bacterial Infections and Mycoses Blood-Borne Infections Central Nervous System Diseases Central Nervous System Fungal Infections Central Nervous System Infections Communicable Diseases Cryptococcosis Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections Meningitis Meningitis, Cryptococcal Meningitis, Fungal Mycoses Nervous System Diseases Neuroinflammatory Diseases RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

21 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Princess Marina Hospital,Bamalete Lutheran Hospital and Scottish Livingstone Hospital

Gaborone,Ramotswa,Molepolole, Botswana

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Early antiretroviral therapy

Other

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.

Primary outcomes

  1. Change in the CSF CFUs between the immediate and standard ART initiation groups

    Time frame: 4 weeks

Secondary outcomes

  1. Grade 3 or 4 adverse events

    Time frame: 6 months

    each participant is followed up for 6 months after the initiation of HAART

  2. Clearance of C. neoformans antigen from CSF and blood.

    Time frame: 6 months

  3. Change in the number of peripheral blood mononuclear cells responding to C. neoformans

    Time frame: 4 weeks

Sponsors and collaborators

Lead sponsor

Botswana-UPenn Partnership

Other

Collaborators

  • Doris Duke Charitable Foundation
  • University of Pennsylvania

Registry information

Official study title

A Randomized Clinical Trial of Immediate Versus Standard Antiretroviral Therapy for HIV-infected Adults Presenting With Cryptococcal Meningitis

Acronym: Crypto

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Sep 14, 2009
Registry last updated
Feb 7, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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