RoutineCryptococcal Screening in Nyanza Province, Kenya

Jeremy Penner

XIXth International AIDS ConferenceTUSA08, 24 Jul 2012

Outline

• Setting• Screening protocol• Treatment protocol• Intervention uptake• Patient outcomes

Family AIDS Care and Education Services

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 treatmentprotocol sent to site

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

Uptake: Routine Program Data

Enrolled

CD4 Documented

CD4 ≤ 100

sCrA

g Docu

mented

sCrA

g +

Fluco

nazole

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000Only 68% of new enrollees had CD4 documented in lab database

10,385

15,260

1,865108

1,72679

Uptake: Chart Reviews from 2 Districts

Enrolled

CD4 Documented

CD4 ≤ 100

sCrA

g Docu

mented

sCrA

g +

Fluco

nazole

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

5,000 4,7574,348

806 508

53 47

91% had CD4performed

63% had sCrAgperformed 89% received

fluconazole

Overall Uptake:53%

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)

Eligibility and EnrollmentAll new enrollees

12,211

No information18 (0.1%)

Child <15 years 2,680 (22%)

CD4≤1001,595 (17%)

CD4>1007,118 (75%)

CD4 not done399 (4%)

File missing401 (4%)

Adult ≥ 15 years 9,513 (78%)

Charts abstracted1,547 (97%)

Dead 383 (25%)Alive 877 (57%)

Transfer 169 (11%)Unknown 118 (8%)

1,222 person-years follow-up

ResultsControln=771

Interventionn=776

p

Age (years) 34 35 .94

Female 55% 53% .42

Body Mass Index 18.6 18.8 .40

CD4+ T-cell count (cells/μl) 45 41 .35

Started on ART during follow up period

76% 77% .63

Time between enrollment and ART initiation (weeks)

4 4 .08

Received anti-tuberculosis medication

27% 23% .10

Kaplan-Meier Survival Curve Comparing Control to Intervention

HR=1.1, p=.41

HR=1.0 [0.9, 1.3]

Survival Curves Comparing sCrAg + to sCrAg - in Intervention Group

HR=1.06, p=.09

HR=1.6 [1.0, 2.7]

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

Acknowledgements• Crypto team:

– Ana-Claire Meyer– Caroline Kendi– Noel Odhiambo– Benard Otieno– 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