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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

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

Brief Summary:

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.


Detailed Summary:
Sponsor: University of Zimbabwe

Current Primary Outcome: 12- month survival in CrAg-positive persons vs. CrAg-negative persons screened [ Time Frame: 12 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: University of Zimbabwe

Dates:
Date Received: April 24, 2015
Date Started: April 2015
Date Completion: June 2017
Last Updated: October 25, 2016
Last Verified: October 2016