Antiretroviral therapy eligibility at enrollment and time to treatment initiation in Ethiopia

 Chloe A. Teasdale1, Chunhui Wang1, Sileshi Lulseged1, Tamrat Assefa1, Solomon 

Ahmed3, Zelalem Habtamu4, Matthew R. Lamb1, Zenebe Melaku1, Elaine J. Abrams1 for the Identifying Optimal Models of HIV Care in Africa study

1ICAP-Columbia University, Mailman School of Public Health, New York, USA; 2Centers for Disease Control and Prevention, Addis Ababa, Ethiopia;

3Oromia Regional Health Board, Ethiopia Ministry of Health, Oromia, Ethiopia

Abstract: A-641-0395-09770This research supported by PEPFAR through the US Centers for Disease Control and Prevention under the terms of Cooperative Agreement Number 5U62PS223540 and 5U2GPS001537

Background (1)• 11.7 million adults and children received ART in low and middle income countries in 20131 Over 7.5 million patients on treatment in sub-Saharan Africa

• Timely initiation of ART is critical before advanced clinical or immunologic disease status reached Late ART initiation associated with increase risk of opportunistic infections and mortality2 

WHO treatment guidelines raised CD4 eligibility criteria in 2010 and 2013 to maximize treatment benefits3 

1UNAIDS 2013; 2SMART 2008, When to Start 2009, Severe 2010;3WHO 2013

Background (2)

• Estimated that only 65% of eligible patients start treatment in RLS1– Many lost to follow-up (LTF) or die prior to ART initiation2 

• Retention and monitoring of patients not eligible for treatment at enrollment into care is challenging– Half of patients who are healthy at enrollment are lost before ART eligibility or initiation3 

1Mugglin 2012; Rosen 2011; 2McGrath 2010, Geng 2012, Aliyu 2013; 3Krazner 2012

HIVTesting

ART eligibility assessment

Linkage to HIV care

Not eligible

Eligible for ART

Pre-ARTPre-ART

ART

Routine monitoring

ART initiation

ART initiation

Enroll in HIV care

HIV-positive

Purpose of Study• Analysis of pre-ART outcomes for adult patients based on ART eligibility status at enrollment in HIV care in Ethiopia Incidence of reaching ART eligibility for patients not eligible for treatment at enrollment

Incidence ART initiation for patients eligible at enrollment and those not eligible at enrollment but reached eligibility during follow-up

Factors associated with ART initiation

• Routinely collected data from ICAP-supported care and treatment sites in Ethiopia Identifying Optimal Models for HIV Care in Africa study Data abstracted from patient charts, de-identified and entered into on-site electronic databases

Methods (1)• All adults > 15 years enrolled in HIV care 2006 to 2011• 45 health facilities, 4 Regions in Ethiopia • ART eligibility at enrollment assessed using CD4 and WHO stage data– 3 groups: eligible, ineligible, indeterminate (insufficient data) 

• Follow-up visit data used to identify date of ART eligibility & ART initiation 

Ethiopia ART guidelines 2003-2012*• WHO stage 4 regardless of CD4+• CD4+ <200/mm3

• CD4+ 200-350 and WHO stage 3

*Ethiopian national ART guidelines changed August 2012

Methods (2)• Cumulative incidence of reaching ART eligibility and ART initiation

• Competing risk regression used to assess factors associated with ART initiation – Models adjusted for known predictors

Enrollment to ART eligibility

Enroll in HIV care

Eligible for ART

Initiate ART

1. Time from enrollment in care to ART eligibility among patients ineligible or indeterminate at  enrollment

Eligibility to ART initiation

2. Time from ART eligibility to ART initiation among patients eligible at enrollment or became eligible

Enrollment eligibility status:

Eligible N=37,801 (51.7%)

IneligibleN=26,204 (35.8%)

IndeterminateN=9,172 (12.5%)

Age(yrs) median (IQR) 32.0 [IQR: 28.0-40.0] 30.0 [IQR: 25.0-37.0] 30.0 [IQR:25.0-38.0]Female 21,161 (56.0) 17,565 (67.0) 5,649 (61.6)Point of entry into care     VCT 11,291 (29.9) 9,566 (36.5) 3,077 (33.6)     PMTCT 540 (1.4) 1,467 (5.6) 347 (3.8)     Inpatient/TB 3,765 (10.0) 1,698 (6.5) 796 (8.7)     Outpatient 10,195 (27.0) 5,821 (22.2) 2,235 (24.4)     Other/unknown 12,010 (31.8) 7,654 (29.2) 2,717 (29.6)WHO stage (missing) 1,031 (2.7) 0 (0) 3,199 (34.9)     I 3,931 (10.4) 15,883 (60.6) 0 (0)     II 5,744 (15.2) 5,580 (21.3) 2,813 (30.7)     III 20,859(55.2) 4,741 (18.1) 3,160 (34.5)     IV 6,236 (16.5) 0(0) 0 (0)CD4 count (missing) 12.949 (34.3) 8,700 (33.2) 7,865 (85.8)     <200 23,544 (62.3) 0 (0) 0 (0)     200-349 1,095 (2.9) 7,685 (29.3) 483 (5.3)     >350 213 (0.6) 9,819 (37.5) 824 (9.0) Median CD4 (IQR) 107.0 [IQR: 55.0-167.0] 376.0 [IQR: 274.0-532.0] 386.0 [IQR: 282.0-539.0]Primary health facility 1,963 (5.2) 1,969 (7.5) 831 (9.1)Rural facility 2,529 (6.7) 1,727 (6.6) 1,025 (11.2)

Selected adult patient characteristics (N=73,177)

Cumulative incidence of reaching ART eligibility for patients ineligible or indeterminate at enrollment (N=35,376)

Competing risk estimators accounting for informative censoring 

At 12 months after enrollment:• 23% of patients ineligible at enrollment

reached ART eligibility • 35% of indeterminate patients reached ART

eligibilityIndeterminate

Ineligible

Enrollment to ART eligibilityEnroll in

HIV careEligible for ART

0.1

.2.3

.4.5

.6.7

.8.9

1

0 3 6 9 12 15 18 21 24month

eligible ineligible indeterminate

Cumulative incidence of ART initiation among adult patients by enrollment eligibility group (N=49,125)

At 1 month from ART eligibility: • 66% of patients eligible at enrollment started ART• 47% of patients who were ineligible at enrollment &

reached eligibility started ART• 66% of patients who were indeterminate at enrollment &

reached eligibility started ART

Eligibility to ART initiationEligible

for ARTInitiate

ART

0.1

.2.3

.4.5

.6.7

.8.9

1

0 3 6 9 12 15 18 21 24month

eligible ineligible indeterminate

Cumulative incidence of ART initiation among adult patients by enrollment eligibility group (N=49,125)

At 3 months from ART eligibility: • 76% of patients eligible at enrollment started ART• 57% of patients who were ineligible at enrollment &

reached eligibility started ART• 75% of patients who were indeterminate & reached

eligibility started ART

Eligibility to ART initiationEligible

for ARTInitiate

ART

0.1

.2.3

.4.5

.6.7

.8.9

1

0 3 6 9 12 15 18 21 24month

eligible ineligible indeterminate

Cumulative incidence of ART initiation among adult patients by enrollment eligibility group (N=49,125)

At 6 months from ART eligibility : • 82% of patients eligible at enrollment started

ART• 64% of patients who were ineligible at

enrollment & reached eligibility started ART• 81% of patients who were indeterminate &

reached eligibility started ART

Eligibility to ART initiationEligible

for ARTInitiate

ART

2006 2007 2008 2009 2010 20110

50

100

150

200

250

300

350

400

450

Median CD4 count at enrollment and ART initiation by year (N=44,211)

Median CD4 at enrollment increased from 141 cell/ml3 to 233 from 2006-2010Median CD4 at ART initiation did not significantly increase

All patients 

Med

ian

CD4+ Enrollment CD4

ART initiation CD4

141

233

112147

2006 2007 2008 2009 2010 20110

50

100

150

200

250

300

350

400

450

Enrollment CD4

Median CD4 count at enrollment and ART initiation by eligibility group and year of ART initiation (N=44,211)

Eligible at enrollment

Med

ian

CD4+

94141

106113ART initiation CD4

2006 2007 2008 2009 2010 20110

50

100

150

200

250

300

350

400

450

Enrollment CD4

Enrollment CD4

Median CD4 count at enrollment and ART initiation by eligibility group and year of ART initiation (N=44,211)

ART initiation CD4

Median CD4 at enrollment increased for ineligible patients 2006-2011Patients still enrolling and starting ART with CD4 <200 (eligibility criteria unchanged)

Ineligible at enrollment            Eligible at enrollment

Med

ian

CD4+

323

94

232

141

427

212

106113

ART initiation CD4

Factors associated with starting ART among all patient who reached eligibility

• Multivariable competing risk regression models significant predictors of starting ART– Older age

• 25-39 vs. 15-24yrs, aSHR*=1.2 (95% CI: 1.2-1.3)• 40-49 vs. 15-24yrs, aSHR=1.3 (95% CI: 1.2-1.4)• 50+  vs. 15-24yrs, aSHR=1.3 (95% CI: 1.2-1.3)

– Lower CD4+ count• <100 vs. >350, aSHR=3.2 (95% CI: 2.8-3.5)• 100-199 vs. >350, aSHR=3.5 (95% CI: 3.2-3.9)• 200-350 vs. >350, aSHR=2.3 (95% CI 2.1-3.0)

*aSHR: adjusted sub-distributional hazard model (using competing risk estimators)

Strengths & Limitations• Strengths

Routine HIV care and treatment program data abstracted from patient charts  Representative, non-study settings 

Large cohort of >73,000 patients 

• Limitations Missing data

40% missing CD4+ and 5% missing WHO stage at enrollment Cannot identify reasons for individual patient management 

Only analyzed those retained in care  Do not know outcomes for lost to follow-up prior to eligibility and ART initiation

LTF is differential based on eligibility status at enrollment

Summary• Many patients eligible for ART at enrollment started treatment– 65% started ART within 1 month, 76% started within 3 months and 82% started within 6 months

• Patients ineligible for ART at enrollment not rapidly initiated on ART after reaching eligibility – Only 64% started ART within 6 months after eligible 

• Many patients still enrolling and many initiating ART with advanced disease status– Median CD4 at enrollment and ART initiation in 2011: 233 and 147 cell/ml3, respectively

Conclusions • Ethiopia has achieved success in scale up of HIV testing, care and treatment services 

• Greater efforts needed to ensure• Continued retention and monitoring of patients in care to identify when they become eligible 

• Rapid initiation of treatment once patients are ART eligible • Avoid late start of ART (CD4<200) 

• New ART eligibility guidelines (CD4 <350) will likely reduce ART initiation at advanced disease status 

THANK YOU

Special thanks to all of the patients and staff at the health facilities and to the ICAP team in Ethiopia who supported 

the health facilities 

Thanks also to the Ethiopia Ministry of Health, CDC and PEPFAR for their support of ICAP and Optimal Models.