Introduction:The case control study was conducted using a convenience method conducted at Mubende enrolled was conducted246 participants 123 participants who had failed on first line(cases) and 123 who had not failed on first line(controls).A supplied convenience method was used. The objectives were:To determine the socio demographic, clinical and personal factors associated with failure of first line ART among the positive clients attending Mubende ART clinic. Results: Majority of the variables were significantly associated with first line treatment failure as reported. Majority of the clients who participated where between 36-45 years(35.8%) while a few who were between 18-25 years (14.2%)failed. Many of the participants who failed were female (54%) and also a big number were widowed (37%).. Participants who did not have formal education are identified to have failed (43.9%). Those who are civil servants (36.6%) were identified to have failed more than other categories. Those clients who were earning more than one hundred thousand shillings (54.2%) were identifies to have failed more than those who earn a monthly income less than 100000/= Area of residence, gender age, monthly income, occupation and marital status were highly associated with failing on first line drugs (p<0.05). Clinical factors were all significantly associated with treatment failure these included :baseline cd4(p<0.001),distance from clients homes(p<0.001),duration on ART(p<0.001),WHO stage(p<0.001),.apart from clinic waiting time(p=0.004) and NVP exposure(p=0.540) and drug availability at the site(p=0.086). and the Personal factors were all significantly associated with first line treatment failure apart from community support groups availability (p=0.883) Recommendations: The Government should put more funding in drug procurement so that there is the strategy of test and treat is initiated this will help to reduce on the HIV transmission rates, reduce on morbidity and mortality rates due to HIV, early initiation will help to improve client s health and hence prolonged stay on first lineetc. In conclusion there are many factors that bring about first line treatment failure there for the government should strengthen the comprehensive HI care and management system.

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