Routine Cryptococcal Screening in Nyanza Province, Kenya

1. RoutineCryptococcal Screening in Nyanza Province, Kenya Jeremy Penner XIXth International AIDS Conference TUSA08, 24 Jul 2012

2. Outline • Setting • Screening protocol • Treatment protocol • Intervention uptake • Patient outcomes

3. Family AIDS Care and Education Services

5. Screening Protocol • All new enrollments • Hematology sample for baseline CD4 to central lab • Serum for RPR also part of baseline specimens • Lab reflex testing, starting Nov 2009 • If enrollment CD4 ≤ 100 cells/μl, perform latex agglutination for sCrAg • If sCrAg + (titre ≥ 1:2) • Results and treatment protocol sent to site

6. Treatment Protocol “This patient has tested positive for cryptococcal infection…should be treated with…” • Fluconazole • 1,200mg x 2 weeks • 800mg x 8 weeks • 200mg maintenance • ART • At 2 weeks if asymptomatic • At 6 weeks if signs/symptoms of meningitis

7. Uptake: Routine Program Data

8. Uptake: Chart Reviews from 2 Districts 91% had CD4 performed Overall Uptake: 53% 63% had sCrAg performed 89% received fluconazole

9. Outcomes: Methods • Inclusion criteria: Newly enrolling adults with CD4 count ≤ 100 cells/μl • Intervention group: • Enrolled between 1 Nov 09 & 31 May 10 • Historical control: • Enrolled between 1 Apr 09 & 31 Oct 09 • Primary endpoint: All-cause mortality • Analysis: Cox proportional hazards • Censored at date of death, last clinic visit, or home visit (for those confirmed alive)

10. Eligibility and Enrollment All new enrollees 12,211 No information 18 (0.1%) Adult ≥ 15 years 9,513 (78%) Child <15 years 2,680 (22%) File missing 401 (4%) CD4≤100 1,595 (17%) CD4>100 7,118 (75%) CD4 not done 399 (4%) Charts abstracted 1,547 (97%) Dead 383 (25%) Alive 877 (57%) Transfer 169 (11%) Unknown 118 (8%) 1,222 person-years follow-up

11. Results

12. Kaplan-Meier Survival Curve Comparing Control to Intervention HR=1.0 [0.9, 1.3] HR=1.1, p=.41

13. Survival Curves Comparing sCrAg + to sCrAg - in Intervention Group HR=1.6 [1.0, 2.7] HR=1.06, p=.09

14. Summary • Limited uptake • CD4: capacity of central labs; lab networking • sCrAg: stock-outs; lab staff turn-over; workload • Fluconazole: early deaths before starting treatment • Documentation • Overall survival not improved compared to historical control • Poor uptake • Treatment may not be adequate • Survival of sCrAg + patients better than expected if no intervention

15. Acknowledgements • Crypto team: • Ana-Claire Meyer • Caroline Kendi • Noel Odhiambo • BenardOtieno • Edwin Omondi • Elizabeth Opiyo • Patrick Oyaro • Elizabeth Bukusi • Craig Cohen • FACES staff and patients, esp the Social Science Department • Ministries of Health, Government of Kenya • Institutions: • Kenya Medical Research Institute • University of California San Francisco • US Centers for Disease Control and Prevention, Kenya • University of British Columbia • This work was supported by: • President’s Emergency Plan for AIDS Relief (U62/CCU924511) • American Academy of Neurology Foundation Practice Research Training Fellowship • Fogarty International Clinical Research Fellowship (5 R24 TW00798; 3 R24 TW00798-02S1) • Hellman Family Foundation