Background: In resources limited countries because of social stigma issues, depression and intentional non adherence do exist. Optimal adherence to HAART (>95%) in People Living with HIV (PLW-HIV) is difficult. Therefore there is a need to evaluate the severity of depression, its association to HAART adherence and Adverse Drug Reactions( ADRs) related to HAART in PLW-HIV in India. Methods: A prospective observational study was carried out in south Indian teaching Hospital in Manipal. Patients were enrolled and informed consent was obtained. As per the inclusion criteria administered with two questionnaires; PHQ 9 Questionnaire and ACTG Adherence Questionnaire. Enrolled Patients were assessed for assessment of severity of depression using PHQ 9 Questionnaire and using ACTG adherence questionnaire. Results were analyzed using Chi-Square test find out the association between adherence and its impact on depression. Reported ADRs were also analyzed based on WHO's and Naranjo’s causality assessment, severity, predictability and preventability Scales. Results: Total 150 patients were enrolled in the study, out of which 33 patients had mild depression 27(81.8%) followed by moderate 3(9%), followed by moderately severe 3(9%) depression with HAART and 146(97.3%) patients were reported to have adherence rate more than 95% for HAART. Number of depression cases with HAART was higher in males 27(81.8%) compared to females 6(18.2%). A significant association between PHQ 9 outcomes 117(100%) (p value <0.005) and patients on HAART without depression was found. 52(34.7%) of the patients was prescribed with Tenofovir+Efavirenz+Lamivudine. 39(26%) patients reported ADRs to HAART, Out of which 5(12.8%) patients reported Efavirenz induced depression, Other ADRs were Zidovudine induced anemia 7(17.9%), Tenofovir induced acute kidney infection 5(12.8%) and Lamivudine induced Skin Rashes 3(7.6%). Conclusion: The impact of depression and its association to HAART needs to be emphasized. Awareness on medication adherence to HAART is essential in People living with HIV In India.