CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa (CryptoART)
|ClinicalTrials.gov Identifier: NCT02434172|
Recruitment Status : Completed
First Posted : May 5, 2015
Last Update Posted : October 12, 2018
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.
|Condition or disease||Intervention/treatment|
|Cryptococcal Meningitis||Other: Pre-emptive screening and treatment for cryptococcal disease|
|Study Type :||Observational|
|Actual Enrollment :||1333 participants|
|Official Title:||The CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa Through Early Detection and Prevention of Cryptococcal Disease|
|Study Start Date :||April 2015|
|Actual Primary Completion Date :||June 2017|
|Actual Study Completion Date :||June 2017|
There are no arms to the study. All participants will undergo screening. Preemptive treatment will only be provided to those who are CrAg positive.
Other: Pre-emptive screening and treatment for cryptococcal disease
Preemptive screening for cryptococcal disease among individuals with CD4 counts below 100 cells/mm3 with anti fungal therapy for those what are Cryptococcus antigen positive. These participants will be followed longitudinally for 12 months to determine clinical outcome, with their outcome compared with similar patients who are cryptococcal antigen negative, who will also be followed longitudinally for 12 months.
- 12- month survival in CrAg-positive persons vs. CrAg-negative persons screened [ Time Frame: 12 months ]
- Seroprevalence of asymptomatic cryptococcal antigenemia among individuals with CD4≤100 cells/mm3 in an urban population in Zimbabwe [ Time Frame: 24 months ]
- Sensitivity, specificity, positive and negative predictive values of point-of-care urine CrAg LFAs [ Time Frame: 24 months ]
- Sensitivity, specificity, positive and negative predictive values of point-of-care whole blood CrAg LFAs [ Time Frame: 24 months ]
- Proportion of individuals with CD4≤100 cells/mm3 and a positive CrAg assay who have disseminated cryptococcal infection with either blood infection or CSF involvement [ Time Frame: 24 months ]
- 12-month survival among individuals with CD4≤100 cells/mm3 prior to implementation of CrAg screening program using historical controls [ Time Frame: 24 months ]Retrospective analysis
- Cost of implementation of CrAg screening among individuals with CD4≤100 cells/mm3 [ Time Frame: 24 months ]
- Cryptococcus-associated mortality among individuals with CD4≤100 cells/mm3, [ Time Frame: 24 months ]
- Incidence of cryptococcal and non-cryptococcal IRIS [ Time Frame: 24 months ]
- Barriers to uptake of diagnostic LP by individuals with asymptomatic cryptococcal antigenemia. [ Time Frame: 24 months ]Questionnaire will be administered to participants who are serum cryptococcal antigen positive who decline to undergo LP.
- Inflammatory cytokines and functional impairments in antigen specific T cells that are associated with the development of cryptococcal antigenemia and meningitis. [ Time Frame: 24 months ]Analysis will be done by ELISA and Luminex assays, cell culture and flow cytometry techniques, data collected will be entered into a database and analyzed by patient characteristics.
- Impact of ART mediated immune reconstitution on the inflammatory cytokine profile and the cryptococcal antigen specific CD4+ T cell response in those with serum and CSF cryptococcal antigenemia compared with those without. [ Time Frame: 24 months ]Analysis will be done by ELISA and Luminex assays, cell culture and flow cytometry techniques, data collected will be entered into a database and analyzed by patient characteristics. Data will be longitudinal including baseline characteristics and subsequent follow-up data at 6 months and 12 months.
Biospecimen Retention: Samples Without DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02434172
|Principal Investigator:||Chiratidzo E Ndhlovu, MBBS, MSc||University of Zimbabwe College of Health Sciences|
|Principal Investigator:||Azure T Makadzange, MD DPhil||Massachusetts General Hospital|