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

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

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

The ARK model

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.

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

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

Results: Objective 1 Baseline characteristics (n= ) Median age, y (IQR) 34 (29-40) Female, n (%) (68.2) CD4 count median (IQR)113 (57-166) WHO stage, n (%) I and II5 326 (24.1) III (63.5) IV2 718 (12.3) Year of enrolment, n (%) (6.3) (18.3) (32.5) (42.9) Province, n (%) Western Cape (39.8) Eastern Cape1 583 (5.4) Kwazulu-Natal (53.0) Mpumalanga523 (1.8)

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

Results Objective 1: ART program outcomes Retention in care (RIC) Virological suppression (VLS) Losses to follow-up (LTFU) Died Months on ART Proportion with VLS(%)86.8 ( ) 87.5 ( ) 87.2 ( ) Probability of RIC (%)80.9 ( ) 72.6 ( ) 68.8 ( ) Proportion LTFU (%) 13.6 ( ) 15.4 ( ) 8.8 ( ) Probability of death (%) 6.3 ( ) 7.4 ( ) 7.8 ( )

Results Objective 1: ART program outcomes Smoothed instantaneous hazard 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

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 ( ) 1.02 ( ) IV 4.34 ( ) 1.68 ( ) Baseline CD4 count ≥ ( ) 1.28 ( ) ( ) 1.77 ( ) < ( ) 1.89 ( ) Year of starting ART ( ) 3.02 ( ) ( ) 4.65 ( ) ( )5.83 ( ) Province Western Cape 11 Eastern Cape2.65 ( ) 0.78 ( ) Kwazulu-Natal2.03 ( ) 1.22 ( ) Mpumalanga2.44 ( ) 1.98 ( )

Baseline factors associated with suboptimal virological response (≥400copies/ml) at 6 months (n= 6 638) O.R. (95% CI) P – value Age (years) ( ) ( ) ( ) < WHO Clinical stage stage I/II 1 stage III1.19 ( ) stage IV 1.04 ( ) Baseline CD4 count ≥ ( ) ( ) < ( ) Province Western Cape 1 Eastern Cape2.35 ( ) < Kwazulu-Natal1.82 ( ) < Mpumalanga5.56 ( ) a <0.0001

Results Objective 1: ART program outcomes Virological suppression of adolescents

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

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 Most comparative published studies followed patients up till similar time.

Results Objective 2: Comparative programs

Results Objective 2: Comparisons with other programs Retention in care

Results Objective 2: Comparisons with other programs Cumulative mortality

Results Objective 2: Comparisons with other programs 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

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

Results; Objective 3: TB treatment comparison ARK supported: 11 sites; 2822 patients Non-ARK supported: 98 sites; patients non-ARKARK ≥ 6m/yrARK ≥ 9m/yrARK 12 months/yr P < Proportion cured: 13.2% at ARK- supported sites (CI %) Proportion defaulted: 42.8% at ARK- supported sites (CI %) Non-ARK

Results Objective 3: TB Rx outcomes: Pre entry vs. post entry Proportion cured: 21.6% (CI %) Proportion defaulted: 30.0% (CI %)

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.) < < (0.73–0.81) (0.64–0.76) < < (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)

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.

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.

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