1. Dorina Onoya 1, Cornelius Nattey 1, Eric Budgell 1, Liudmyla van den Berg 2, Denise Evans 1, Mhairi Maskew 1, Kamban Hirasen 1, Lawrence Long 1, Matthew P Fox 1,3,4 1 Health Economics and Epidemiology Research Office, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa; 2 Right to Care, Johannesburg, South Africa 3 Department of Global Health, Boston University School of Public Health, Boston, MA, USA; 4 Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA PHASA Conference, East London, 19 - 22 September 2016 Contextual and adherence related predictors of virologic failure among patients on second-line antiretroviral therapy in South Africa

2. Background Globally, the scale up of ART in resource limited settings has resulted in substantial reductions in morbidity and mortality and increased life expectancy for PLHIV Demand for first and second-line ART continues to grow as ART coverage increases in SA 23-36% VL failure by 12 months on second line ART – compared to 8-23% by 5 years on first line ART If these rates are sustained, Increased demand for very expensive third-line regimens Increased pressure on already constrained budgets

3. Figure 1. Second line ART guideline changes in South Africa from 2004 to 2015 TDF-3TC/FTC-LPV/r 2010 GUIDELINES TDF-3TC/FTC-LPV/r AZT/ABC-3TC-LPV/r 2013/2015 GUIDELINES TDF-3TC/FTC-ATV/r AZT/ABC-3TC-ATV/r AZT/ABC-3TC-LPV/r AZT-ddI-LPV/r 2004 GUIDELINES Failing TDF based 1 st line Failing d4T/AZT based 1st line Failing on d4T-3TC-EFV/NVP Failing TDF based 1 st line Failing d4T/AZT based 1st line LPVr adverse reaction on 2 nd line

4. Objectives In this study we examined predictors of virologic failure among HIV positive patients switched to second line ART in Johannesburg, South Africa Specifically (this analysis): 1.Contextual/social determinants 2.Adherence-related predictors

5. Methods Study design: Case-control study at Themba Lethu clinic (TLC Study population: HIV positive adults who switched to a standard second-line ART at TLC since 01 April 2004 At risk for a first virologic failure on second-line in December 2013 onwards Cases and controls Cases: Patients who failed second-line ART (two consecutive VL>1000 copies/ml) Controls comes from population that gave rise to cases (never failed on second line) Study participants asked to respond to questions about events occurring: Cases: 1 month before date of failure Controls: 1 month before date of last viral load test

6. Methods Sample size: 70 cases + 130 controls ( enrolled between Dec 2014 and Jan 2016) Inclusion criteria: Adult patients (≥18 years) Failed standard first-line ART ≥ 01 April 2004 Initiated standard 2 nd -line ART at TLC ≥ 01 April 2004 At risk for first VL failure on second line in Dec 2013 Met definition of case or control Provided informed consent Exclusion criteria: Not healthy enough to be interviewed Previously enrolled as a case (controls can become cases) Failed second-line before Dec 2013

7. Analytic methods Unconditional logistic regression to estimate OR & 95% CI Developed an index of social instability based on patients’ living arrangement, food insecurity, employment, sexual partnership status and dwelling types Additional self reported variables: demographic information, access to clinic, experience with HIV treatment, experiences of adverse drug reaction (ADR) and coping with side effects, adherence self efficacy, depression, alcohol use and disclosure of HIV status Clinical measures (clinic file/lab data): ADR (any one) reported up to 6 months prior to the date of VL failure for cases or the interview date for controls.

8. Results Among both cases and controls the majority of participants were female (60.0% and 54.6% for cases and controls respectively). 76% of participants were between 31 and 50 years old and over 80% had at least a secondary school level of education Younger patients ( 30 years OR=3.6, 95% CI (1.2- 7.8) Patient who were dependent on public transportation or went to the clinic on foot were at higher odds of VL failure as compared OR= 5.2, 95% CI ( 1.4- 13.5)

9. Results The odds of VL failure was higher among patients who experienced high social Instability compared to those with low social Instability OR= 2.9, 95% CI( 1.9-4.3) Participants who reported having missed 10% or more of their ARV doses, were 4.6 times more likely to experience VL failure 95% CI (2.1 -10.0) If you reported ADR, disclosed to friends & colleagues, were depressed and drank alcohol were all associated with increased odds of VL failure Non of clinical factors ( Regimen at failure, creatinine clearance, haemoglobin, CD4, who stage, BMI ) were predictive of VL failure

10. Figure 2. Summary and proposed framework of predictors of virologic failure among patients on second line ART in Johannesburg, South Afr ica  Age (<30 years)  High social instability  Self-reported ADR  Disclosure to friends and colleagues only  Medium/high depression  Alcohol use (>5 drinks per month)  Working all day  Moves on foot /public Transport ≤90% adherence Virologic failure

11. Discussion Results suggest complex social and economic factors contributing to drug adherence and subsequent risk of VL failure among patient on 2 nd line therapy in South Africa Identifying patients with markers of social instability and adherence challenges could facilitate targeted interventions to decrease the risk of 2 nd line treatment failure

12. Limitations Limited statistical power Recall bias: Cases asked to respond to questionnaire about circumstances / events occurring 1 month before date of failure (may be as far back as Dec 2013) Controls asked to respond based on circumstances / events occurring 1 month before last VL test