The CryptoART Study: Decreasing Mortality Associated With Initiation of Antiretroviral Therapy in Sub-Saharan Africa Through Early Detection and Prevention of Cryptococcal Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,333
- 试验地点
- 1
- 主要终点
- 12- month survival in CrAg-positive persons vs. CrAg-negative persons screened
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
12- month survival in CrAg-positive persons vs. CrAg-negative persons screened
时间窗: 12 months
次要结局
- Cost of implementation of CrAg screening among individuals with CD4≤100 cells/mm3(24 months)
- Incidence of cryptococcal and non-cryptococcal IRIS(24 months)
- Barriers to uptake of diagnostic LP by individuals with asymptomatic cryptococcal antigenemia.(24 months)
- Sensitivity, specificity, positive and negative predictive values of point-of-care whole blood CrAg LFAs(24 months)
- 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.(24 months)
- Seroprevalence of asymptomatic cryptococcal antigenemia among individuals with CD4≤100 cells/mm3 in an urban population in Zimbabwe(24 months)
- Sensitivity, specificity, positive and negative predictive values of point-of-care urine CrAg LFAs(24 months)
- Cryptococcus-associated mortality among individuals with CD4≤100 cells/mm3,(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(24 months)
- 12-month survival among individuals with CD4≤100 cells/mm3 prior to implementation of CrAg screening program using historical controls(24 months)
- Inflammatory cytokines and functional impairments in antigen specific T cells that are associated with the development of cryptococcal antigenemia and meningitis.(24 months)
研究者
Chiratidzo Ndhlovu
Associate Professor of Medicine
University of Zimbabwe