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NCT Number: NCT02434172

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

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.

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Key information

Conditions

Cryptococcal Meningitis Bacterial Infections and Mycoses Central Nervous System Diseases Central Nervous System Fungal Infections Central Nervous System Infections Cryptococcosis Infections Meningitis Meningitis, Cryptococcal Meningitis, Fungal Mycoses Nervous System Diseases Neuroinflammatory Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Parirenyatwa Hospital

Harare, Zimbabwe

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Pre-emptive screening and treatment for cryptococcal disease

Other

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.

Primary outcomes

  1. 12- month survival in CrAg-positive persons vs. CrAg-negative persons screened

    Time frame: 12 months

Secondary outcomes

  1. Seroprevalence of asymptomatic cryptococcal antigenemia among individuals with CD4≤100 cells/mm3 in an urban population in Zimbabwe

    Time frame: 24 months

  2. Sensitivity, specificity, positive and negative predictive values of point-of-care urine CrAg LFAs

    Time frame: 24 months

  3. Sensitivity, specificity, positive and negative predictive values of point-of-care whole blood CrAg LFAs

    Time frame: 24 months

  4. 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

  5. 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

  6. Cost of implementation of CrAg screening among individuals with CD4≤100 cells/mm3

    Time frame: 24 months

  7. Cryptococcus-associated mortality among individuals with CD4≤100 cells/mm3,

    Time frame: 24 months

  8. Incidence of cryptococcal and non-cryptococcal IRIS

    Time frame: 24 months

  9. 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.

  10. 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.

  11. 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.

Sponsors and collaborators

Lead sponsor

University of Zimbabwe

Other

Collaborators

  • Centers for Disease Control and Prevention

Registry information

Official study title

The CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa Through Early Detection and Prevention of Cryptococcal Disease

Acronym: CryptoART

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
May 5, 2015
Registry last updated
Oct 12, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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