Integrated cryptococcal antigen screening and pre-emptive treatment prior to initiation of antiretroviral treatment in Cambodia

Abstract

Background: Detection of serum cryptococcal antigen (sCrAg) in HIV-infected patients is associated with 3-6 fold increased mortality. Studies on the feasibility and effectiveness of sCrAg-screening and pre-emptive therapy before antiretroviral treatment (ART) are limited. Amongst antiretroviral treatment-naïve adults with baseline CD4 counts <100 cells/μL undergoing pre-ART sCrAg screening, without previous cryptococcal meningitis (CM), we report on the 1) prevalence of sCrAg-positivity; 2) proportion with concurrent CM; 3) six-month patient outcomes. Methods: This is a retrospective hospital-based cohort study evaluating a "screen-and-treat" protocol implemented between 10/2008 and 8/2012 in Phnom Penh, Cambodia. All sCrAg(+) patients underwent lumbar puncture (LP). After ruling-out CM, fluconazole was started (400mg/d-10 weeks; 200mg/d secondary prophylaxis) immediately. sCrAg(-) patients received primary prophylaxis (fluconazole 100mg/d). CM was treated with amphotericin-B (0.7mg/ kg-2 weeks, followed by fluconazole 400mg/day for 8 weeks). Results: A total of 357 patients were enrolled with a median age of 38 (IQR 31-43) years and median CD4 count of 28 (IQR 14-53) cells/μL; 54% were male, 20% had BMI <16 kg/m2. Thirty (8.4%) of 357 tested were sCrAg(+). Six (20%) of the 30 sCrAg(+) patients had concurrent CM with no/minimal symptoms. Two were treated as CM without LP done. Amongst sCrAg(+) patients, the following 6-month outcomes were noted: 25 (83.3%) were retained and on ART, 1 (3.3%) patient died and 4 (13.3%) were lost-to-follow-up. Excluding those treated for CM (n=8), one case (1/22; 4.5%) of incident CM was detected by month six. Corresponding 6-month outcomes amongst the 327 CrAg(-) patients were: 269 (82.3%) retained and on ART, 23 (7%) deaths, 29 (9%) lost-to-follow-up, 6 (1.8%) transferred-out. One case (1/327; 0.3%) of incident CM was documented. Conclusion: Outcomes of sCrAg(+) patients with the "screen-and-treat" approach were good. Fluconazole at 400mg/day appears appropriate for treatment of sCrAg(+) patients. Routine LP in sCrAg(+) might be indicated. copy; 2013 Chim B, et al.