Objective: To establish factors contributing to non adherence to antiretroviral therapy (ART) among HIV in-fected clients attending care at Uganda cares Soroti health care center in Soroti regional referral hos-pital. Method: This was a descriptive cross sectional study design involving 133 HIV infected respondents on ART. Respondents were sampled via systematic random method after acquisition of verbal consent. Data was collected using a semi structured and pre-coded researcher administered questionnaire. Data was entered in Epi-data v3.1 and then exported to Epi-Info v3.3.1 for statistical analysis at 95% confi-dence level using chi-square tests, fisher‟s exact test and logistic regression analysis. Results were presented in a tabular and graphical form. Probability values less than 0.05 were considered statisti-cally important Results: 53.4% of the respondents were females, 52.6% were of the age group 40-59 years, 50.4% were mar-ried, and 37.6 % had attained primary level of education. Only 63% of the respondents‟ were adhe-rent to the prescribed ARVs. The most commonly cited factors for non adherence to ART by the respondents were: long waiting hours in the clinic 14.3%, patient health worker relationship 9.1%, financial constrains, distance, & transport cost 8.3%, loosing appointment card 5.3%, 4.5% side ef-fects of the drugs and patient health worker ratio. At bivariate level of analysis, tendency for respon-dents to forget medication swallowing (p<0,001), ARV related side effects (p=0.002), service pro-vider attitude (p=0.004) and routine HIV counseling (p=0.008) were significantly correlated with adherence. However, via multiple logistic regression analysis, forgetting to take ARVs (adjusted OR=42, 95%CI: 5-348, p<0.001) and experience of ARV related side effects (adjusted OR=4, 95%CI: 1-12, p=0.01) were powerfully and significantly associated with non adherence to ART. Conclusion: ARV related toxicities/side effects and patient tendency to forget medication swallowing remarkably accounted for non adherence to ART among clients seeking comprehensive HIV care at Uganda Cares in Soroti Regional Referral Hospital. Recommendation: Early detection, diagnosis and appropriate management of patient related ART side effects in com-bination with new treatment reminder strategies are highly required for patient ART adherence

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