An Enhanced Package of Care to Reduce Mortality in Persons with Advanced HIV Disease

加强一揽子护理以降低晚期艾滋病毒患者的死亡率

• 批准号: 10322279
• 负责人: Radha Rajasingham
• 金额: $ 66.23万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-23 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10322279
• 关键词: Africa South of the Sahara; Antifungal Therapy; Antigens; Biological Assay; Blood; CD4 Lymphocyte Count; Caring; Cells; Cessation of life; Clinic; Clinical; Clinical Trials; Cluster randomized trial; Coupled; Cryptococcal Meningitis; Cryptococcus; Data; Diagnostic; Disease; Flow Cytometry; Fluconazole; Funding; Guidelines; HIV; Health; Health Personnel; Hospital Costs; Hospitals; Infection; Inflammatory; International; Meningitis; Opportunistic Infections; Performance; Persons; Plasma; Prophylactic treatment; Randomized; Recommendation; Retrospective cohort; Risk; Scotland; Serum; Specificity; Syndrome; Testing; Time; Tuberculosis; Uganda; Venous; Visual; World Health Organization; antiretroviral therapy; care seeking; cost; cost effectiveness; cost-effectiveness evaluation; diagnostic screening; high risk; high risk population; immune reconstitution; improved; isoniazid; lateral flow assay; mortality; novel; point of care; point-of-care diagnostics; randomized trial; rifapentine; screening; screening guidelines; standard of care; transmission process; treatment guidelines; tuberculosis treatment; urinary

Antiretroviral therapy (ART) is recommended for all people living with HIV (PLWH) – regardless of their CD4 cell count – to improve survival and reduce transmission. This “treat-all” approach benefits PLWH overall, but also confers a risk of unmasking immune reconstitution inflammatory syndrome (IRIS) and death, particularly for the 30-40% of people who present with advanced HIV disease (CD4 count <200 cells/µL) worldwide. In 2017, the World Health Organization (WHO) recommended that persons with advanced HIV disease be screened for opportunistic infections (OIs) and given prophylaxis for tuberculosis (TB) and cryptococcal antigen (CrAg). However, because this screening and prophylaxis package has never been validated in a clinical trial, it is not consistently implemented in sub-Saharan Africa. Compounding the problem, funding for CD4 testing has been reduced by stakeholders as CD4 testing is no longer needed for ART initiation. Consequently, identification of persons with advanced HIV disease via CD4 testing and OI screening and prophylaxis often does not occur in reality. As a result, early mortality after ART initiation remains high. Subsequent to the release of the initial 2017 WHO recommendations for OI screening and prophylaxis, several novel point-of-care diagnostics and treatments for OIs have emerged: ● Visitect point-of-care CD4 assay provides a visual result of CD4 count >200 of <200 cells/µL, with a sensitivity of 92% and specificity of 89% in venous blood; ● Semi-quantitative CrAg lateral flow assay (CrAg-SQ LFA) can detect persons with CrAg titers who likely have disseminated infection and are at risk of meningitis/death despite standard of care antifungal therapy; ● Fujifilm SILVAMP TB LAM, a new point-of-care TB urinary test, has 70% sensitivity and 91% specificity; ● Isoniazid (INH) + Rifapentine given for one month for latent TB treatment is non-inferior to 9 months of INH. The objective of this proposal is to improve survival in persons with advanced HIV disease. We will implement a 2x2 factorial, cluster-randomized trial in 24 Ugandan clinics to: (Aim 1) determine the survival benefit of a novel point-of-care CD4 test compared with standard flow cytometry CD4 testing in persons with advanced HIV disease; and (Aim 2) determine the survival benefit of an enhanced diagnostic OI screening and prophylaxis strategy in persons with advanced HIV disease. The enhanced OI screening and prophylaxis strategy will include point-of-care FujiFilm TB LAM, CrAg-SQ LFA, with enhanced prophylaxis for TB (1 month of INH + rifapentine), and referral of plasma CrAg+ with high titers to hospital. Survival and retention-in-care will be assessed at 6 months. Lastly, (Aim 3) we will evaluate the cost and cost-effectiveness of the CD4 testing strategies (described in Aim 1) and OI screening and prophylaxis strategies (described in Aim 2). Findings from this trial will have the potential to impact international HIV treatment guidelines on optimal management of persons with advanced HIV disease in order to reduce HIV-related mortality globally.

建议对所有艾滋病毒感染者（PLWH）进行抗逆转录病毒治疗（ART），无论其CD4水平如何