CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa

University of Zimbabwe

Status: Completed

Conditions: Cryptococcal Meningitis

Treatments: Other: Pre-emptive screening and treatment for cryptococcal disease

Study type: Observational

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02434172

1U01GH000737-01

Details and patient eligibility

About

The study will determine if the initiation of a 'screen and treat' program for cryptococcal disease among HIV positive individuals decreases morbidity and mortality among individuals with CD4 count < 100 cells/mm3. The study will screen individuals who are asymptomatic for CM and are either ART naïve or ART experienced with CD4 count < 100 cells/mm3.

The introduction of an cheap, easy to use point of care diagnostic test the lateral flow assay will facilitate rapid diagnosis of cryptococcal disease in resource limited settings. The investigators will determine the efficacy of the lateral flow assay in identifying latent and asymptomatic cryptococcal disease. The investigators will determine the efficacy of the test in detecting disease in readily available body fluids such as urine and whole blood obtained via finger-stick method. The investigators will also determine the cost effectiveness of a screen and treat approach for cryptococcal disease in Zimbabwe.

The investigators also wish to understand why some individuals with low CD4 counts reactivate cryptococcal disease and screen positive for cryptococcal antigen (CrAg) while others with similar levels of immunocompromised do not.

Enrollment: 1,333 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented HIV positive test by standard national algorithm
• CD4 count ≤100 cells/mm3
• Age > 18 years
• Residence within 50 km of Harare
• Able to provide written informed consent

Exclusion criteria

• Presence of clinical symptoms suggestive of meningitis.
• Recent history of CM within 2 weeks of enrollment, i.e., participants within the induction phase of therapy.
• Individuals with severe hepatic injury, jaundice, alanine transferase (ALT) >5x upper limit of normal
• Individuals with renal failure, defined by an estimated Glomerular filtration rate (eGFR) ≤30 mL/min (using MDRD (Modification of Diet in Renal Disease) equation)
• Currently known to be pregnant
• A negative urine pregnancy test is required for study entry for women with childbearing potential.
• The use of contraception will be recommended to women with childbearing potential while on high dose fluconazole therapy. Referral to family planning services will be given as necessary.
• Previous allergy or other reaction to amphotericin B and/or fluconazole
• Currently enrolled in another clinical trial/study

Trial design

1,333 participants in 1 patient group

Screening

Description:

There are no arms to the study. All participants will undergo screening. Preemptive treatment will only be provided to those who are CrAg positive.

Treatment:

Other: Pre-emptive screening and treatment for cryptococcal disease