1. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Factors related to non-adherence to antiretroviral (ART) drugs among adult ART clients attending 18 facilities in Tanzania, Uganda and Zambia Julie Denison, FHI360 Olivier Koole, Institute of Tropical Medicine

2. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Study Team FHI 360, USA Muhimbili University of Health and Allied Sciences, Tanzania Infectious Diseases Institute, Makerere University Medical School, Uganda Tropical Diseases Research Centre, Zambia Institute of Tropical Medicine, Belgium Massachusetts General Hospital, USA Centers for Disease Control and Prevention, USA Gideon Kwesigabo Fred Wabwire-Mangen Modest Mulenga Julie Denison Sharon Tsui Cindy Geary Meng Wang Ya Diul Mukadi Leine Stuart Eric Van Praag Kwasi Torpey Joris Menten Robert Colebunders Olivier Koole David Bangsberg Andrew Auld Simon Agolory Seymour Williams Jonathan Kaplan Aaron Zee

3. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Context Massive ART scale-up: 8 million people on ART High levels of ART adherence required for viral suppression and good clinical outcomes Adherence levels higher in sub-Saharan Africa – Mills et al pooled estimate: 55% N. America; 77% SSA (JAMA 2006) – Nachega et al (Curr Opin HIV/AIDS 2010)

4. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Objectives Primary To characterize the current level of adherence among ART clinic patients across multiple program settings Secondary To identify important factors associated with ART adherence, including both individual risk factors and program characteristics

5. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Study Population and Sites Study Population – 18+ years at ART initiation at study site – Initiated 3 ARVs at least 6 months prior to data collection Study sites – 3 countries – 6 sites per country, purposively selected UGANDA TANZANIA ZAMBIA

6. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Methods Adherence Self-reports: 3-day, 30-day, 30- day VAS, Case Index Provider estimates: 30-day Pharmacy data: medication possession ratio (mpr) Known risk factors Stigma, depression, alcohol use, social support, disclosure, wealth index Pre ART CD4 count, WHO Stage, ART regimen, pill burden, number of years on ART Cross-sectional design: 250 patients per site systematically selected April-August 2011

7. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Methods Viral load testing conducted at six sites June to July 2011, Health Care Manager questionnaire conducted at 18 sites – Rural/Urban – Level and type of health facility – Community ART dispensing – ART initiation requirements – Stockouts – Type of clinic staff (i.e. Lay counselors)

8. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Analysis 1.Adherence levels described with cutoff points determined by ROC curve analysis using HIV viral load (VL) =1,000 copies/ml 2.Optimal adherence measures selected based on degree of association with viral load failure 3.Multivariate regression analysis, adjusted for site- level clustering, assessed associations between non- adherence and individual and program factors

9. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Patient Accounting Number of ART clients screened6,825 Number of ineligible ART clients1,854 Initiated ART <6 months before study1,529 Less than age 18 729 Did not speak a study language 783 Number of eligible ART clients4,971 Number who did not consent482 Number who consented and are in the analysis4,489 CountryNumber of sitesNumber of participants Tanzania71498 Uganda61495 Zambia61496

10. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Selected Participant Characteristics Characteristic4,489 n (%) Age (year), mean (SD) 40.9 (9.4) Sex, Female3,045 (67.8) Years on ART < 21,102 (24.6) 2-52,249 (50.1) >51,138 (25.4) Pre-ART CD4 <=2503,020 (67.3) >250567 (12.6) Missing902 (20.1) Characteristic4,489 n (%) Current ART regimen d4T(30),3TC,NVP 731 (16.3) TDF,3TC/FTC, EFV 699 (15.6) AZT,3TC,EFV 773 (17.2) AZT,3TC,NVP 1,427 (31.8) Other 684 (15.2) Missing 175 (3.4)

11. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Selected Program Characteristics Characteristicn Total number of clinics 19 Setting Rural/peri-urban6 Urban13 Number of adults on ART < 20008 2000-40007 > 40004 Characteristicn Level of health facility National referral4 Provincial/Regional4 District6 Primary/ community based 5 Type of health facility Government10 Mission5 Non-religious NGO4

12. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 1. Levels of Incomplete Adherence 9.9% (148/1,496) had VL >1000 copies/ml VL failure ranged from 7.2%- 17.2% by study site

13. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 1. Levels of Incomplete Adherence Adherence measure ROC Cutoff n/N% Incomplete Adherence 3-day 93%340/43977.7 30-day 99%611/438713.9 30-day VAS 99%2401/445054.0 Case Index 11751/447316.8 Health provider98%2617/441559.3 Pharmacy MPR90%1634/407040.1

14. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 2. Selection of Adherence Measures: Associations with Viral Load Failure Adherence measure CategoryVL Failure >1,000 copies/ml OR (95% CI) Self-Report 3-day <93% 1.40 (0.80,2.46) > 93% 30-day<99%1.13 (0.71,1.78) >99% 30-day VAS <99%0.86 (0.57,1.30) >99% Case Index <111.30 (0.84, 2.01) >11

15. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 2. Selection of Adherence Measures: Associations with Viral Load Failure Adherence measureCategoryVL Failure >1,000 copies/ml OR (95% CI) Provider Report<98%1.57(1.02,2.41) >98% Pharmacy MPR <90%1.48 (1.02,2.15) >90%

16. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 3. Model Building: Bivariate Incomplete Adherence Pharmacy MPR Individual characteristics Significant and selected (p<0.1)Non –significant and not selected (p>0.1) -Female sex -Younger than 35 years -On ART between 2-5 years -Greater internalized stigma -Positive screen for depression -Taking four or more pills daily -Missing pre-ART CD4 count -Marital Status -Social support -CAGE alcohol abuse -DHS Wealth Index -Cost to clinic -Time to clinic -Disclosure -Pre-ART WHO-stage

17. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 3. Model Building: Bivariate Incomplete Adherence Pharmacy MPR None of the Program characteristics were significant at p<0.2 -Level of health facility -Type of health facility -Dispensing of ARVs at community level -Buddy needed for ART initiation -Lay counselor provides adherence counseling -ART stock out (past six months) -Location (urban/rural)

18. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 3. Model Building: Multivariable Incomplete Adherence Pharmacy MPR Adjusted Odds Ratios (95% CI) Age >350.85 (0.73-0.99) Years on ART <21 2-51.21 (1.02-1.43) 5+0.88 (0.72-1.10) Stigma High1.26 (1.06-1.50) Pill Burden 4+ daily1.35 (1.12-1.62) Pre-ART CD4 Missing1.37 (1.15-1.63)

19. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Conclusions Wide variability in adherence levels Pharmacy MPR and provider estimates associated with VL failure Interventions needed to – Reach younger ART clients – Support long-term adherence – Address internalized stigma

20. www.ias2013.org Kuala Lumpur, Malaysia, 30 June - 3 July 2013 Special thanks to our funders, partners, study clinics and ART clients