The impact of routine cryptococcal antigen screening on survival among HIV-infected individuals with advanced immunosuppression in Kenya

被引:32
|
作者
Meyer, A. -C. L. [1 ,2 ]
Kendi, C. K. [1 ]
Penner, J. A. [1 ,3 ]
Odhiambo, N. [1 ]
Otieno, B. [1 ]
Omondi, E. [1 ]
Opiyo, E. [1 ]
Bukusi, E. A. [1 ]
Cohen, C. R. [4 ]
机构
[1] Kenya Govt Med Res Ctr, Family AIDS Care & Educ Serv, Res Care & Training Program, Ctr Microbiol Res, Nairobi, Kenya
[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA
[3] Univ British Columbia, Dept Family Practice, Vancouver, BC V5Z 1M9, Canada
[4] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA
基金
美国国家卫生研究院;
关键词
cryptococcus; screening; prevention; Africa; outcomes; cryptococcal meningitis; HIGH-DOSE FLUCONAZOLE; CLINICAL PRESENTATION; ANTIRETROVIRAL THERAPY; EARLY MORTALITY; MENINGITIS; SERUM; DIAGNOSIS; ADULTS; AIDS; THAILAND;
D O I
10.1111/tmi.12067
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Objectives To test the hypothesis that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV-infected individuals with low CD4 cell counts. Methods Newly enrolled patients at Family AIDS Care and Education Services (FACES) in Kenya with CD4100 cells/l were tested for serum cryptococcal antigen (sCrAg). Individuals with sCrAg titre1:2 were treated with high-dose fluconazole. Cox proportional hazard models of KaplanMeier curves were used to compare survival among individuals with CD4100 cells/l in the intervention and historical control groups. Results The median age was 34years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/l [IQR: 18,71]. Follow-up time was 1224 person-years. In the intervention group, 66% (514/782) were tested for sCrAg; of whom, 11% (59/514) were sCrAg positive. Mortality was 25% (196/782) in the intervention group and 25% (191/771) in the control group. There was no significant difference between the intervention and control group in overall survival [hazard ratio (HR): 1.1 (95%CI:0.9,1.3)] or three-month survival [HR: 1.0 (95%CI:0.8,1.3)]. Within the intervention group, sCrAg-positive individuals had significantly lower survival rates than sCrAg-negative individuals [HR:1.8 (95%CI: 1.0, 3.0)]. Conclusions A screening and treatment intervention to identify sCrAg-positive individuals and treat them with high-dose fluconazole did not significantly improve overall survival among HIV-infected individuals with CD4 counts100 cells/l compared to a historical control, perhaps due to intervention uptake rates or poor efficacy of high-dose oral fluconazole. Objectifs Tester l'hypothese selon laquelle une intervention de depistage et de traitement tot de l'infection cryptococcique ameliorerait la survie des individus infectes par le VIH ayant un faible taux de cellules CD4. Methodes Les nouveaux patients inscrits aux Services de Soins SIDA et d'education pour la famille (FACES) au Kenya avec des taux de CD4 100cellules/l ont ete testes pour l'antigene cryptococcique serique (sCrAg). Les personnes ayant un titre de sCrAg 1:2 ont ete traitees avec des doses elevees de fluconazole. Des modeles de KaplanMeier de risques proportionnels de Cox ont ete utilises pour comparer la survie chez les individus ayant des CD4 100cellules/l dans les groupes d'intervention et temoin historique. Resultats L'age median etait de 34 ans [IQR: 29.41], 54% etaient des femmes et le taux median de CD4 etait de 43 cellules/l [IQR: 18.71]. La duree de suivi etait de 1224 personnes-annees. Dans le groupe d'intervention, 66% (514/782) ont ete testes pour sCrAg; dont 11% (59/514) etaient sCrAg positifs. La mortalite etait de 25% (196/782) dans le groupe d'intervention et 25% (191/771) dans le groupe temoin. Il n'y avait pas de difference significative entre le groupe d'intervention et le groupe temoin pour la survie globale [Rapport de risque (HR): 1.1 (IC 95%: 0.91.3)] ou pour la survie relative a trois mois [RR: 1.0 (IC 95%: 0.81.3)]. Dans le groupe d'intervention, les individus sCrAg seropositifs avaient des taux de survie limites plus faibles que ceux des individus sCrAg negatifs [RR: 1.8 (IC 95%: 1.03.0)]. Conclusions Une intervention de depistage et de traitement pour identifier les individus sCrAg seropositifs et les traiter avec de fortes doses de fluconazole n'a pas ameliore significativement la survie globale des individus infectes par le VIH dont le taux de CD4 100cellules/l par rapport a un groupe temoin historique, peut-etre en raison du taux d'adoption de l'intervention ou de l'efficacite mediocre des fortes doses de fluconazole par voie orale. Objetivos Evaluar la hipotesis de que una intervencion de cribaje y tratamiento de una infeccion temprana con criptococo puede mejorar la supervivencia de individuos infectados con VIH y con un bajo conteo de celulas CD4. Metodos A los nuevos pacientes de los servicios de Cuidados Familiares para SIDA y Educacion (FACES) en Kenia con CD4 100celulas/l se les realizo una prueba para el antigeno del Criptococo en suero (sCrAg). A los individuos con un titulo de sCrAg 1:2 se les trato con una dosis alta de fluconazol. Se utilizaron modelos de riesgos proporcionales de Cox de curvas de Kaplan-Meier para comparar la supervivencia entre individuos con CD4 100celulas/l en los grupos de intervencion y el control historico. Resultados La media de edad era de 34 anos [IQR: 29.41], 54% eran mujeres, y la media de CD4 era 43celulas/l [IQR: 18.71]. El tiempo de seguimiento era de 1224 personas-anos. En el grupo de intervencion a un 66% (514/782) se les realizo la prueba para sCrAg, de los cuales un 11% (59/514) eran sCrAg positivos. La mortalidad era del 25% (196/782) en el grupo de intervencion y del 25% (191/771) en el grupo control. No habia una diferencia significativa en la supervivencia total entre el grupo de la intervencion y el grupo control [Hazard Ratio (HR): 1.1 (IC 95%:0.9.1.3)] o en la supervivencia a tres meses [HR: 1.0 (IC 95%:0.8.1.3)]. Dentro del grupo de intervencion, los individuos sCrAg positivos tenian tasas de supervivencia inferiores, comparados con los individuos negativos para sCrAg [HR:1.8 (IC 95%: 1.0, 3.0)]. Conclusiones Una intervencion de cribaje y tratamiento para identificar a los individuos positivos para sCrAg y tratarlos con una dosis alta de fluconazole, no mejoro de forma significativa la supervivencia total entre los individuos infectados con VIH con conteos de CD4 100celulas/l comparado con un control historico, tal vez debido a las tasas de aceptacion de la intervencion o a la mala eficacia de las dosis altas de fluconazol oral.
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页码:495 / 503
页数:9
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