Introduction: India has the second highest number of AIDS cases in the world but there is paucity of data on drug resistance mutations. There are some specific mutations that occur in patients harboring clade C virus. Tuberculosis is a common confection in these patients. We describe a male patient aged 38 years, with heterosexually acquired clade C who reported 12 years ago with high viral load and a CD 4 cell count of 28/mm3. He posed a formidable challenge to the physician when only two drugs were available. His hemoglobin dropped to 4 gms% after zidovudine administration, developed 4 episodes of TB of different organs, 2 episodes of candida, single episode of pneumocystis pneumonia and repeated treatment failure over a period of 11years. He had a total of 17 mutations; 8 at 7 NRTI sites, 4 at 3 NNRTI sites and 5 at 4 PI sites, uncommon combination of TAMI and other typical clade C mutations and was resistant to most NRTI and NNRTI drugs. He was finally put on a five drug regimen including four protease inhibitors in 2008 and is doing well. He had to spend personally more than 2.3 million Indian Rupees (50000 US dollars) in 10 years to fight the onslaught of rapidly mutating virulent virus. Conclusion: In a resource constrained setting one may be forced to resort to a suboptimal medication in a desperate attempt to save the patient as in this case. We were able to prolong life but at a price as he was resistant to most NRTI and NNRTI drugs. There is a dire need for a cost effective, simple method to identify drug resistance mutations in resource poor countries for a rational approach to therapy. It high lights the economic burden in era of HAART and future strategies required to curtail resistance mutations. This case also gives an insight into the pitfalls of treatment of tuberculosis in patients suffering from AIDS. In our experience splenic tuberculosis in HIV positive individuals could be considered as an AIDS defining disease.