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Identifying Novel Mechanism of Protease Resistance among Patients Failing Second Line HAART in South India

Principal Investigators
Dr T. R. Dinesha
Funding Agency


  • To study the rate of second-line treatment failure (TF) with and without Protease Resistance (PR) drug resistance mutations (DRMs);
  • To find the prevalence of alternative resistance mutation in circulating RNA in the absence and presence of PR DRMs;
  • To identify the naturally occurring substrate polymorphisms by examining HIV-1 infected ART naïve subjects


With the aim of ending AIDS epidemic, UNAIDS has launched momentous target of 90-90-90 by 2020, which aims for 90% of HIV patients to be diagnosed for HIV, of which 90% should be initiated treatment and of which 90% should achieve suppressed viral load. With this ambitious goal in mind, WHO has emphasised that Highly Active Antiretroviral Therapy (HAART) should be initiated to all HIV patients diagnosed (“test and treat” strategy), which has been recently implemented in India as well. With the increased access to ART, formidable development is required in the area of treatment monitoring. Due to this strategy, the number of people on second-line HAART has also started showing an increasing pattern. Unlike development of resistance to first-line HAART in direct drug target, the resistance to second-line HAART develops both in direct drug target (PR) and its substrates (Gag and Gag-pol precursors). Growing evidence also suggests that up to 65% of second-line failures do not develop drug resistance mutation (DRM) in PR, but harbor DRM in Gag Cleavage Site (Gag-CS) and non Cleavage Site (non-CS). The routine assay in current use to monitor drug resistance does not include Gag and Gag-pol precursors. In this present study, we aim to study the DRM in PR and PR substrates such as CS and non-CS sites of Gag in second-line failures and will correlate the co-evolution of PR mutation with its substrate mutation. In addition to that, PR and Gag-CS and non-CS mutation will also be studied in the ART naïve participants. As many patients have already been on Protease inhibior/ritonavir (PI/r) in India, understanding the frequency of alternative resistance mutation will help us to accurately measure PI resistance. Thus, through this study, HIV monitoring system can be strengthened thereby we can limit the emergence of mutation and preserve limited drug options for future therapy.