The impact of routine cryptococcal antigen screening on survival among HIV-infected individuals with advanced immunosuppression in Kenya
Tropical Medicine and International Health
Family AIDS Care and Education Services, Research Care and Training Program, Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya; Department of Neurology, University of California San Francisco, San Francisco, CA, United States; Department of Family Practice, University of British Columbia, Vancouver, BC, Canada; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA, United States
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 CD4 ≤ 100 cells/μl were tested for serum cryptococcal antigen (sCrAg). Individuals with sCrAg titre ≥ 1:2 were treated with high-dose fluconazole. Cox proportional hazard models of Kaplan-Meier curves were used to compare survival among individuals with CD4 ≤ 100 cells/μl in the intervention and historical control groups. Results: The median age was 34 years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/μl [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 counts ≤ 100 cells/μl compared to a historical control, perhaps due to intervention uptake rates or poor efficacy of high-dose oral fluconazole. © 2013 Blackwell Publishing Ltd.
cryptococcal antigen; fluconazole; fungus antigen; unclassified drug; acquired immune deficiency syndrome; antigen; bacterium; disease treatment; drug; epidemiology; fungal disease; human immunodeficiency virus; hypothesis testing; meningitis; mortality; serum; survival; womens health; adult; article; CD4 lymphocyte count; controlled study; cryptococcosis; drug megadose; female; human; Human immunodeficiency virus infected patient; immune deficiency; Kenya; major clinical study; male; mortality; overall survival; survival rate; Adult; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antifungal Agents; Antigens, Fungal; Case-Control Studies; CD4 Lymphocyte Count; Cryptococcus neoformans; Female; Fluconazole; Humans; Kaplan-Meier Estimate; Kenya; Male; Meningitis, Cryptococcal; Survival Rate; Treatment Outcome; Kenya