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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

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Validating five questions of antiretroviral non-adherence in a decentralized

public-sector antiretroviral treatment program in rural South Africa

Krisda Chaiyachati1-3, Lisa R Hirschhorn4,5, , Frank Tanser2, Marie-Louise Newell2,6, Till Bärnighausen2,3

1Yale Primary Care Internal Medicine Residency Program, New Haven and Waterbury, Connecticut; 2Africa Centre for Health and Population Studies, University of KwaZulu-Natal, South Africa;

3Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts; 4Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts;

5John Snow Institute, Research and Training, Boston, Massachusetts; 6Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London, UK





  • Five assessments of ART adherence administered were:
    • 7-day recall of missed doses
    • 7-day recall of late doses (missed by >2 hours)
    • A six-level Likert scale of adherence (“excellent” to “very poor”)
    • 30-day visual analogue scale (VAS, proportion of pills missed)
    • Question on the last dose missed within seven discrete time periods.
  • Questions were validated in their performance to detect treatment failure at 6 months:
    • Immunologic failure: CD4 <100 cells/mm3 after 6 months (+/- 45 days) of ART
    • OR
    • 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 < 35 years), and education level (> or < secondary education)
  • 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
  • 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


  • 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


  • 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


  • 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


  • A public sector, decentralized ART program in rural KwaZulu-Natal, South Africa between 2007-08


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. 2011 Mar; 25(3): 163-70.