The patients initiated on Antiretroviral treatment (ART) and if adherence is good can continue on first line ART for a number of years. However, over the years some percentage of People Living with HIV(PLHIV) on first line ART develops resistance to these drugs due to mutations in virus. Patients suspected of treatment failure on first line ART based on WHO defined immunologic, clinical and definitive virologic failure qualify for switch to second–line ART. With the increase in number of patients on first line therapy it is envisioned that a proportion of patients will experience treatment failure and need second line ART regimens over time. In 2008, National AIDS Control Organization (NACO) piloted a national strategy for the provision of free second–line ART in India and these drugs are being provided free of cost  at 10 Centres of Excellence and their linked ART Plus Centres. As on August 2015, 12,823 patients were receiving second line drugs in the National programme [1].This study was done to observe the clinical, immunological, virological and survival of patients on second–line ART under programmatic condition.   Materials and Methods: Study site: This observational study was conducted at the ART Centre of the Centre of Excellence (COE),Gandhi Hospital, Secunderabad. The ART centre is one of the largest in this region with 14,024 PLHIV registered in HIV care and 5,076 currently on first line ART.COE is also a referral centre for evaluation of patients suspected of first line failure from 7 other ART centres. Study population: Data of all patients >15 years of age who were started on second–line therapy due to failure of first line ART at COE Gandhi Hospital during JAN2013 to December 2013 were included in this study. The first line regimen recommended by NACO and received by patients was Zidovudine + Lamivudine + Nevirapine if hemoglobin was >9gm/dl or Tenofovir+Lamivudine + Nevirapine if hemoglobin <9gm/dl. Efavirenz was substituted for Nevirapine in those taking anti–tubercular drugs and those with Nevirapine toxicity.   Patients on first line therapy were eligible for evaluation for second–line ART if they had been receiving ART for at least 6 months, and had demonstrated treatment adherence of >95 %, and had WHO clinical or immunological failure as per NACO guidelines. Viral load estimation was done in these patients and those with HIVRNA >5,000 copies/mL (Oct 2010) were considered as first–line failure and started on second line therapy [2].In March 2014, the cut off level of viral load for starting ART was reduced to >1000 copies/ml by NACO.   All patients with first line failure between JAN 2013 and DEC 2013 were given a uniform second–line ARTregimen provided by NACO comprising of Tenofovir (TDF) + Lamivudine (3TC)+Atazanavir/ritonavir (ATV/r). Tenofovir (TDF) replaced by Zidovudine (AZT)if patient not taken Zidovudine (AZT) in previous history and Hemoglobin >9 g/dL. Atazanavir/ritonavir (ATV/r) replaced by Lopinavir/ritonavir (LPV/r) in patients with significant hyperbilirubinemia (serum total Bilirubin is > 7 mg/dl or the Child–Pugh Score is ≥ 7)or  HIV–2.In patients with concomitant tuberculosis rifampicin was replaced by rifabutin without any change in the ART regimen         PLHIV were followed up monthly and CD4 count was done 6 monthly for all patients. During each visit, patients were counselled for adherence and evaluated for drug toxicity, clinical improvement and opportunistic infections. Patient’s weight, clinical stage, functional status, drug toxicity, adherence to ART medication, presence of opportunistic infection, any change in therapy were documented. Viral load (VL) was repeated by COBASTaqMan HIV–1 assay in all patients at 6 months, if itwas<400copies/ml at 6 months it was not repeated further as per National guidelines. Patients with VL >400copies/ml at 6 months, adherence was reinforced and VLwas repeated at 12 months. Adherence was calculated on the basis of pill count at every visit by the formula: Number of pills actually taken by a patient for a particular time period/Number of pills prescribed for this time period × 100. For analysis we compared those with >95 %adherence at every visit with those with <95 % at any visit. At the end of the month patients were labelled as ‘ontreatment’ if they picked up their drugs, ‘missed’ if they did not pick up drugs for the month, ‘dead’ if they expired and ‘transferred out’ if they were transferred out to another ARTcentre. Those patients who did not come for 3 consecutive months were labelled as ‘lost to follow up (LFU)‘at the end of fourth month as per NACO guidelines.   Results: One twenty four patients were started on second line ART (TDF/ZDV+3TC+Atv/Rtv) between January 2013 to December 2013. At the end of follow up, out of 124 patients started on second line therapy, 17 (13.7%) had expired.The most common cause to switch on second–line ART was combined immunological and virologic failure.