Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Doris Duke Charitable Foundation | OTHER |
| University of Pennsylvania | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Early antiretroviral therapy | Experimental | Subjects randomized to this arm will initiate antiretroviral therapy within 7 days of enrollment. |
|
| Standard antiretroviral therapy | No Intervention | Subjects randomized to this arm will initiate antiretroviral therapy approximately 4 weeks after enrollment. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the CSF CFUs between the immediate and standard ART initiation groups | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Grade 3 or 4 adverse events | each participant is followed up for 6 months after the initiation of HAART | 6 months |
| Clearance of C. neoformans antigen from CSF and blood. | 6 months |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Gregory P Bisson, MD,MSCE | Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania | Principal Investigator |
| Pablo Tebas, MD | Botswana-UPenn Partnership, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Princess Marina Hospital,Bamalete Lutheran Hospital and Scottish Livingstone Hospital | Gaborone,Ramotswa,Molepolole | Botswana |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23362285 | Derived | 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. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D016919 | Meningitis, Cryptococcal |
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D016921 | Meningitis, Fungal |
| D020314 | Central Nervous System Fungal Infections |
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Change in the number of peripheral blood mononuclear cells responding to C. neoformans | 4 weeks |
| D007239 | Infections |
| D003453 | Cryptococcosis |
| D002494 | Central Nervous System Infections |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008581 | Meningitis |
| D000090862 | Neuroinflammatory Diseases |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |