Validating five questions of antiretroviral non-adherence in a decentralized public-sector antiretroviral treatment program in rural South Africa Krisda Chaiyachati 1-3, Lisa R Hirschhorn 4,5,, Frank Tanser2, Marie-Louise Newell 2,6, Till Bärnighausen 2,3 1 Yale Primary Care Internal Medicine Residency Program, New Haven and Waterbury, Connecticut; 2 Africa Centre for Health and Population Studies, University of KwaZulu-Natal, South Africa; 3 Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts; 4 Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts; 5 John Snow Institute, Research and Training, Boston, Massachusetts; 6 Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK BackgroundMethodsResultsSummary Medication adherence is important for treatment success, especially for chronic conditions like HIV Instruments to measure ART adherence identify patients needing treatment support, preventing treatment failure and the development of resistance Simple questions are often used to measure ART adherence in sub-Saharan Africa (SSA) Self-reported adherence tools have rarely been independently validated Objective Limitations Citation Five assessments of ART adherence administered were: 1.7-day recall of missed doses 2.7-day recall of late doses (missed by >2 hours) 3.A six-level Likert scale of adherence (“excellent” to “very poor”) 4.30-day visual analogue scale (VAS, proportion of pills missed) 5.Question on the last dose missed within seven discrete time periods. Questions were validated in their performance to detect treatment failure at 6 months: 1.Immunologic failure: CD4 <100 cells/mm 3 after 6 months (+/- 45 days) of ART OR 2.Virologic failure: VL >400 copies/ml after previously undetectable VL or VL >10,000 copies/ml after 6 months (+/- 45 days) of ART Sensitivities and specificities in predicting treatment failure at 6 months were calculated. Further analyses of performance: At 3 months and beyond 6 months Combining immunologic or virologic failure as a possible outcome Combinations of highly sensitive (screen) then highly specific (confirm) questions Stratification by sex, age (> or or < secondary education) Enrollment Cross-sectional approach Alternative reasons for treatment failure: Primary and secondary HIV resistance Malabsorption or vomiting Drug interactions, especially tuberculosis or traditional medication Lag time between adherence and treatment response Table 1. Sample Characteristics CD4 count sampleVL sample N=165N=137 Female (%)7681 Age [median (IQR)]38 (33-44) Level of education None (%)109 Primary school (%)3028 Secondary school or higher (%)6063 Travel time to clinic in minutes [median (IQR)]30 (15-40)30 (20-40) Disability grant for HIV (%)4547 Disclosure of HIV status to family or friend (%)100 Time on ARV in months [median (IQR)]14 (9-25) Treatment failure Immunologic failure (%)7- Virologic failure (%)-9 IQR, Interquartile Range Table 2. Sensitivity & Specificity in Detecting Immunologic Failure Question item Non-adherence Number reporting non-adherence SensitivitySpecificity cutoff(95% CI) CD4 count sample (N=165) 7-day recall of missed doses <95%60 (0-26)96 (92-99) <85%10 (0-26)99 (96-100) <75%10 (0-26)99 (96-100) 7-day recall of late doses (>2 hours) <95%50 (0-26)97 (93-99) <85%10 (0-26)99 (96-100) <75%00 (0-2)100 (74-100) A six-level Likert item <Excellent (74-100)5 (2-9) <Very Good7342 (15-72)55 (47-63) <Good1125 (5-57)95 (90-98) 30-day VAS <95%70 (0-26)95 (91-98) <85%00 (0-2)100 (74-100) <75%00 (0-2)100 (74-100) Last missed dose <Never2717 (2-48)84 (77-89) <1 month100 (0-26)93 (88-97) <2 weeks10 (0-26)99 (96-100) Table 3. Sensitivity & Specificity in Detecting Virologic Failure Question item Non-adherence Number reporting non-adherence SensitivitySpecificity cutoff(95% CI) VL sample (N=137) 7-day recall of missed doses <95%40 (0-25)97 (92-99) <85%00 (0-3)100 (75-100) <75%00 (0-3)100 (75-100) 7-day recall of late doses (>2 hours) <95%40 (0-25)97 (92-99) <85%10 (0-25)99 (96-100) <75%00 (0-3)100 (75-100) A six-level Likert item <Excellent13192 (64-100)3 (1-8) <Very Good5923 (5-54)55 (45-64) <Good78 (0-36)95 (90-98) 30-day VAS <95%30 (0-25)98 (93-100) <85%10 (0-25)99 (96-100) <75%00 (0-3)100 (75-100) Last missed dose <Never228 (0-36)83 (75-89) <1 month60 (0-25)95 (90-98) <2 weeks10 (0-25)99 (96-100) The Likert item screened immunologic or virologic failures best, but with poor specificity Altering the time of follow-up, combining outcomes or questions, and stratification did not significantly improve the performance of adherence questions Validate the performance of five commonly used ART adherence questions against a gold standard of treatment failure Inclusion: ART experienced >2 weeks, viral load (VL) or CD4 count within 6 weeks of enrolment, and age > 18 years Excluded: Pregnant individuals or anticipated ART discontinuation within 6 months Chaiyachati K, Hirschhorn LR, Tanser F, Newell ML, Bärnighausen T. Validating five questions of antiretroviral nonadherence in a public-sector treatment program in rural South Africa. AIDS Patient Care STDS Mar; 25(3): Conclusions No single question or combination of questions had sensitivity and specificity appropriate for screening purposes and resource allocation, respectively Valid tools for measuring adherence are urgently needed in SSA to identify patients for treatment support and those at risk of treatment failure These lessons can extend to the management of non-communicable diseases Setting A public sector, decentralized ART program in rural KwaZulu-Natal, South Africa between