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

Abstract

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.

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.

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)].

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.