1. Good Three-year Outcomes of Antiretroviral Therapy at Multiple NGO- assisted facilities in Four Provinces in South Africa Geoffrey Fatti, Ashraf Grimwood & Peter Bock Absolute Return for Kids South Africa

2. Background ARK SA: NPO established in November 2003 Mission: To reduce HIV/AIDS related orphan hood by improving ART access to parents and carers at a primary healthcare level in a sustainable manner, in partnership with government

3. Background Overall program outputs: Nov 08 111 ARK-supported sites in four provinces in SA: Western Cape, Eastern Cape, Kwazulu-Natal, Mpumalanga 61 995 ARV patients enrolled at ARK-supported sites ~ 10% of patients enrolled in the public sector

4. The ARK model

5. Aim and Objectives Aim: Evaluate the ARK ART clinical services program Objectives: 1.a - Report ART program outcomes at all ARK- supported sites in SA. b - Identify baseline patient factors associated with poor outcome. 2.Compare outcomes with other programs - Sub-Saharan Africa -developed countries. 3.TB treatment outcomes: Compare ARK-assisted sites vs. non ARK-assisted TB treatment facilities.

6. METHODS Objective 1: ART program outcomes Sample population: All ART-naïve adults ( ≥16) starting ART at facilities supported by ARK between November 2003 and December 2007 Outcome measures: Death, loss to follow-up (LTFU) & virological suppression (VLS) Definitions: Time measured from date of ART initiation until date of last follow-up visit. LTFU: absence from site of more than three months beyond last missed appointment date. VLS: viral load < 400 copies/ml

7. METHODS Objective 1: ART program outcomes Statistical methods: Kaplan-Meier estimates of mortality and retention in care calculated Smoothed instantaneous hazard curves of death and LTFU plotted using weighted kernel density estimates Multivariable competing-risks Cox regression and logistic regression: -baseline patient factors associated with death, LTFU and suboptimal virological response (< 400 copies/ml) after 6 months of ART

8. Results: Objective 1 Baseline characteristics (n= 29 319) Median age, y (IQR) 34 (29-40) Female, n (%)19 995 (68.2) CD4 count median (IQR)113 (57-166) WHO stage, n (%) I and II5 326 (24.1) III13 996 (63.5) IV2 718 (12.3) Year of enrolment, n (%) 20041 846 (6.3) 20055 375 (18.3) 20069 514 (32.5) 20072 582 (42.9) Province, n (%) Western Cape11 673 (39.8) Eastern Cape1 583 (5.4) Kwazulu-Natal15 540 (53.0) Mpumalanga523 (1.8)

9. Results Objective 1: ART program outcomes Baseline CD4 cell count per calendar year Proportion with baseline CD4 < 50, and WHO Stage IV

10. Results Objective 1: ART program outcomes Retention in care (RIC) Virological suppression (VLS) Losses to follow-up (LTFU) Died Months on ART 12 24 36 Proportion with VLS(%)86.8 (85.8-87.8) 87.5 (85.3-89.6) 87.2 (80.6-92.3) Probability of RIC (%)80.9 (80.4-81.4) 72.6 (71.9-73.3) 68.8 (67.8-69.8) Proportion LTFU (%) 13.6 (13.1-14.2) 15.4 (14.5-16.4) 8.8 (6.7-11.3) Probability of death (%) 6.3 (6.0-6.7) 7.4 (7.1-7.8) 7.8 (7.4-8.3)

11. Results Objective 1: ART program outcomes 0.002.004.006.008.01.012 Smoothed instantaneous hazard 061218243036 Months since start of ART. death Loss to follow-up Hazard of death and LTFU Mortality rates: Months 0-6: 11.1 (CI: 10.5–11.7) Months >6: 1.9 (CI: 1.8–2.0) deaths/100 person-years

12. Baseline factors associated with death and loss to follow-up at 6 months (n=15 476) Death; HR (95% CI)Loss to follow-up; HR (95% CI) WHO stage I/II 11 III1.61 (1.29-2.00) 1.02 (0.89-1.18) IV 4.34 (3.38-5.58) 1.68 (1.38-2.04) Baseline CD4 count ≥ 200 11 50-1991.61 (1.09-2.38) 1.28 (0.98-1.67) 25-493.61 (2.40-5.45) 1.77 (1.31-2.40) <254.63 (3.10-6.92) 1.89 (1.40-2.54) Year of starting ART 2004 11 20050.92 (0.70-1.22) 3.02 (1.85-4.96) 20060.72 (0.54-0.96) 4.65 (2.84-7.61) 20070.52 (0.38-0.71)5.83 (3.55-9.57) Province Western Cape 11 Eastern Cape2.65 (1.69-4.16) 0.78 (0.54-1.13) Kwazulu-Natal2.03 (1.67-2.46) 1.22 (1.04-1.44) Mpumalanga2.44 (1.46-4.09) 1.98 (1.28-3.06)

13. Baseline factors associated with suboptimal virological response (≥400copies/ml) at 6 months (n= 6 638) O.R. (95% CI) P – value Age (years) 16-194.10 (1.85-9.15)0.001 20-29 1 30-390.86 (0.72-1.03) 0.119 40-490.62 (0.48-0.78) <0.0001 WHO Clinical stage stage I/II 1 stage III1.19 (0.99-1.45) 0.063 stage IV 1.04 (0.77-1.39) 0.804 Baseline CD4 count ≥100 1 50-1991.03 (0.84-1.26) 0.775 25-490.96 (0.73-1.27) 0.789 <250.89 (0.67-1.18) 0.410 Province Western Cape 1 Eastern Cape2.35 (1.55-3.58) <0.0001 Kwazulu-Natal1.82 (1.48-2.23) <0.0001 Mpumalanga5.56 (3.40-9.13) a <0.0001

14. Results Objective 1: ART program outcomes Virological suppression of adolescents

15. Results Objective 1: ART program outcomes Missing 6m viral load (%) by province Missing 6m viral load (%) by year

16. METHODS Objective 2: Comparison with other programs Literature review of ART program outcomes in low-income and high-income settings. Calendar years of patient follow-up: potential confounder when comparing outcomes. ARK-assisted site subset used for comparisons: patients enrolled & followed until March 2006. Most comparative published studies followed patients up till similar time.

17. Results Objective 2: Comparative programs

18. Results Objective 2: Comparisons with other programs Retention in care

19. Results Objective 2: Comparisons with other programs Cumulative mortality

20. Results Objective 2: Comparisons with other programs 19.8 3.9 1.71.9 2.1 3.3 0 5 10 15 20 25 ARK-assisted sites WCape DOH KhayelitshaART-LINC Loss to follow up at 6 and 12 months (%) 6 months 12 months Loss to follow-up at 6 and 12 months

21. Results Objective 2: Comparisons with other programs Virological suppression at 6 and 12 months

22. Results; Objective 3: TB treatment comparison ARK supported: 11 sites; 2822 patients Non-ARK supported: 98 sites; 32 853 patients 78.7 79.2 80.1 70.7 60 70 80 90 100 non-ARKARK ≥ 6m/yrARK ≥ 9m/yrARK 12 months/yr P < 0.0001 Proportion cured: 13.2% at ARK- supported sites (CI 10.6-15.9%) Proportion defaulted: 42.8% at ARK- supported sites (CI 33.9-50.5%) Non-ARK

23. Results Objective 3: TB Rx outcomes: Pre entry vs. post entry Proportion cured: 21.6% (CI 16.7-26.7%) Proportion defaulted: 30.0% (CI 15.9-41.8%)

24. Results; Objective 3: Duration of ARK involvement at sites and poor TB Rx outcome Treatment failureDefaulted treatment Year Odds ratio* P-value Odds ratio* P-value (95% C.I.)(95% C.I.) 2004-07 0.77 < 0.0001 0.69< 0.0001 (0.73–0.81) (0.64–0.76) 2004 0.56 < 0.0001 0.48< 0.0001 (0.50–0.64) (0.38–0.62) *Odds of poor outcome per additional 6 month period of ARK presence at a site (maximum-likelihood logit estimates for grouped data, adjusted for no. of cases per site)

25. Conclusions Good medium-term ART outcomes are achievable in multiple-site NGO-assisted primary-health facilities ART needs to be initiated at an earlier stage (by increasing access to care) to reduce early on-treatment mortality. Additional adherence support for adolescents is required to improve virological suppression. Increasing loss to follow-up as ART program expands needs to be addressed. Need to improve systems to ensure viral load results are made available, which may including point of care facilities and partnerships with private laboratories. Adherence-supported ART services have a significantly beneficial impact on TB treatment outcomes.

26. Limitations of study Missing viral load results may result in a differential bias in virological suppression proportions in either direction. Comparisons of ART outcomes with other programs are hampered by differences in reporting methods used, baseline immunologic status, cohort selection criteria, duration of and calendar years of monitoring, cohort size, and regimen differences. Improvements in TB treatment outcomes are likely to be due to ART itself and NGO-related site interventions-the relative contributions of each were not measured in this study. Confounders in TB treatment outcomes eg site level HIV prevalence and socio-economic status were not included in analyses.

27. Thank you! Esca Scheepers Eula Mothibi Anita Jason Mokgadi Malahlela ARK trustees, ARK UK & SA colleagues PEPFAR South African Department of Health - for support and input without whom this work would not have been possible. Acknowledgements