1. Antiretroviral therapy eligibility at enrollment and time to treatment initiation in Ethiopia Chloe A. Teasdale 1, Chunhui Wang 1, Sileshi Lulseged 1, Tamrat Assefa 1, Solomon Ahmed 3, Zelalem Habtamu 4, Matthew R. Lamb 1, Zenebe Melaku 1, Elaine J. Abrams 1 for the Identifying Optimal Models of HIV Care in Africa study 1 ICAP-Columbia University, Mailman School of Public Health, New York, USA; 2 Centers for Disease Control and Prevention, Addis Ababa, Ethiopia; 3 Oromia Regional Health Board, Ethiopia Ministry of Health, Oromia, Ethiopia Abstract: A-641-0395-09770 This research supported by PEPFAR through the US Centers for Disease Control and Prevention under the terms of Cooperative Agreement Number 5U62PS223540 and 5U2GPS001537

2. Background (1) 11.7 million adults and children received ART in low and middle income countries in 2013 1  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 mortality 2  WHO treatment guidelines raised CD4 eligibility criteria in 2010 and 2013 to maximize treatment benefits 3 1 UNAIDS 2013; 2 SMART 2008, When to Start 2009, Severe 2010; 3 WHO 2013

3. Background (2) Estimated that only 65% of eligible patients start treatment in RLS 1 – Many lost to follow-up (LTF) or die prior to ART initiation 2 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 initiation 3 1 Mugglin 2012; Rosen 2011; 2 McGrath 2010, Geng 2012, Aliyu 2013; 3 Krazner 2012 HIV Testing ART eligibility assessment Linkage to HIV care Pre-ART ART Routine monitoring ART initiation Enroll in HIV care HIV-positive

4. 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

5. 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 *Ethiopian national ART guidelines changed August 2012

6. 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 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

7. Enrollment eligibility status: Eligible N=37,801 (51.7%) Ineligible N=26,204 (35.8%) Indeterminate N=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] Female21,161 (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) CD4 count (missing) 12.949 (34.3)8,700 (33.2)7,865 (85.8) <200 23,544 (62.3) 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)

8. 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 eligibility Indeterminate Ineligible

9. 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

10. 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

11. 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

12. Median CD4 count at enrollment and ART initiation by year (N=44,211) Median CD4 at enrollment increased from 141 cell/ml 3 to 233 from 2006-2010 Median CD4 at ART initiation did not significantly increase All patients Median CD4+ Enrollment CD4 ART initiation CD4 141 233 112 147

13. Enrollment CD4 Median CD4 count at enrollment and ART initiation by eligibility group and year of ART initiation (N=44,211) Eligible at enrollment Median CD4+ 94 141 106 113 ART initiation CD4

14. 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 2006-2011 Patients still enrolling and starting ART with CD4 <200 (eligibility criteria unchanged) Ineligible at enrollment Eligible at enrollment Median CD4+ 323 94 232 141 427 212 106 113 ART initiation CD4

15. 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 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)

16. 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

17. 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/ml 3, respectively

18. 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

19. 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.