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

NCT ID: NCT00976040

Last Updated: 2012-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2011-12-31

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.

Conditions

Cryptococcal Meningitis; HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early antiretroviral therapy

Subjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment.

Group Type: EXPERIMENTAL

Early antiretroviral therapy

Intervention Type: 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.

Standard antiretroviral therapy

Subjects randomized to this arm will initiate antiretroviral therapy approximately 4 weeks after enrollment.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Doris Duke Charitable Foundation

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Botswana-UPenn Partnership

OTHER

Sponsor Role: lead

Responsible Party

Gregory Bisson

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gregory P Bisson, MD,MSCE

Role: PRINCIPAL_INVESTIGATOR

Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Pablo Tebas, MD

Role: PRINCIPAL_INVESTIGATOR

Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Locations

Princess Marina Hospital,Bamalete Lutheran Hospital and Scottish Livingstone Hospital

Gaborone,Ramotswa,Molepolole, , Botswana

Countries

Botswana

References

Bisson GP, Molefi M, Bellamy S, Thakur R, Steenhoff A, Tamuhla N, Rantleru T, Tsimako I, Gluckman S, Ravimohan S, Weissman D, Tebas P. Early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with HIV and cryptococcal meningitis. Clin Infect Dis. 2013 Apr;56(8):1165-73. doi: 10.1093/cid/cit019. Epub 2013 Jan 29.

Reference Type: DERIVED

PMID: 23362285 (View on PubMed)

Other Identifiers

THE BOTSHELO STUDY

Identifier Type: -

Identifier Source: org_study_id