Risk factors for non-adherence and loss to follow-up in a three-year clinical trial in Botswana

Background

Participant non-adherence and loss to follow-up can compromise the validityof clinical trial results. An assessment of these issues was made in a3-year tuberculosis prevention trial among HIV-infected adults inBotswana.

Methods and Findings

Between 11/2004–07/2006, 1995 participants were enrolled at eightpublic health clinics. They returned monthly to receive bottles ofmedication and were expected to take daily tablets of isoniazid or placebofor three years. Non-adherence was defined as refusing tablet ingestion butagreeing to quarterly physical examinations. Loss to follow-up was definedas not having returned for appointments in ≥60 days. Between10/2008–04/2009, survey interviews were conducted with 83participants identified as lost to follow-up and 127 identified asnon-adherent. As a comparison, 252 randomly selected adherent participantswere also surveyed. Multivariate logistic regression analysis was used toidentify associations with selected risk factors. Men had higher odds ofbeing non-adherent (adjusted odds ratio (AOR), 2.24; 95%confidence interval [95%CI]1.24–4.04) and lost to follow-up (AOR 3.08; 95%CI1.50–6.33). Non-adherent participants had higher odds of reportingdifficulties taking the regimen or not knowing if they had difficulties (AOR3.40; 95%CI 1.75–6.60) and lower odds associated witheach year of age (AOR 0.95; 95%CI 0.91–0.98), but othervariables such as employment, distance from clinic, alcohol use, andunderstanding study requirements were not significantly different thancontrols. Among participants who were non-adherent or lost to follow-up,40/210 (19.0%) reported that they stopped the medication becauseof work commitments and 33/210 (15.7%) said they thought they hadcompleted the study.

Conclusions

Men had higher odds of non-adherence and loss to follow-up than women.Potential interventions that might improve adherence in trial participantsmay include:targeting health education for men, reducing barriers,clarifying study expectations, educating employers about HIV/AIDS to helpreduce stigma in the workplace, and encouraging employers to supportemployee health.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00164281","term_id":"NCT00164281"}}NCT00164281