PURPOSE AND AIM Multi-drug resistance in treatment-experienced human immune deficiency virus (HIV) patients has been a major cause to first line antiretroviral therapy (ART) failure, necessitating a switch to second line therapy. In India, the second line treatment program is still relatively new with little experience and unclear outcomes. It is therefore, critical to assess the clinical, virological and immunological effectiveness and treatment outcome over the 1(st) year of follow-up in the patients' switched to the second line ART at public sector tertiary care center. MATERIALS AND METHODS A prospective, observational study was carried out on HIV positive patients switched on second line ART from January 2010 to December 2010 at ART Centre, Civil Hospital, Ahmedabad. Demographic details, symptoms, adverse drug reactions (ADRs), second line ART regimens, CD4 count, and plasma viral load (PVL) were recorded in a case record form. Patients were followed-up monthly for 12 months. The data was analyzed by t-test, z-test, and Fisher-exact test. RESULTS Out of 126 patients, 82 received regimen V [zidovudine (ZDV) + lamivudine (3TC) + tenofovir (TDF) + boosted lopinavir (LPV/r)] and 44 received regimen Va [3TC + TDF + LPV/r]. A significant (P < 0.0001) increase in mean body weight and marked reduction in number of patients (7) categorized as WHO stage III/IV was observed at 12 months of second line ART. Moreover, a significant immune reconstitution with increase in mean CD4 count and viral suppression (PVL < 400 copies/ml) in 103 (82%) patients (P < 0.0001) was also observed. A total of 83 ADRs were observed in 69 (55%) patients, the most common being dyslipidemia (57) followed by anemia (9). CONCLUSION Early treatment outcome with second line ART was good with 82% success rate in treatment experienced HIV patients. Dyslipidemia and anemia were the common ADRs observed.