The peptide sequence also determines the effectivity of CTL responses it induces and therefore different HLA allotypes can provide varying degrees of protection. For instance, HLA subtypes such as HLAB* 58 and HLA-B*27 provide prolonged protection against HIV-1 infection and are associated with delayed onset of AIDS, while the converse is true of HLA-B*08. Rapid CGP 39551 mutations of the HIV-1 genome due to erroneous HIV Reverse Transcriptase and host RNA processing elements, cause immunity escape mutations to accumulate in the HIV-1 genome. CTL escape mutations may interfere with the processing and presentation of the CTL epitope or attenuate CTL T-Cell receptor interaction with the peptide-MHC complex rendering the epitope ineffective. In the majority of HIV-1 infected individuals, effective immune responses are BNTX maleate mostly transient mainly due to the acquisition of immunity escape mutations by HIV-1. The development of antiretrovirals have provided additional protection against HIV infection. Antiretroviral drugs, such as HIV protease inhibitors and HIV reverse transcriptase inhibitors inhibit steps in the HIV-1 viral replication cycle and have a large negative impact on viral load. Still, ARV resistance can also accumulate, the mechanism involving interference with the binding of an ARV to the target site and rendering the drug ineffective. Previous researchers have provided evidence of interaction between ARV resistance mutations and CTL escape mutations. For example, the HIV-1 protease resistance mutation M46I is a CTL escape mutation of an HLA-A*02 restricted epitope, but also serves as a resistance mutation to the PIs, tripanavir and atazanavir. Another PR mutation, L90M, elucidates an HLA-A*02 restricted epitope spanning the PR positions 76�C84 by inducing an appropriate proteasomal cleavage site. Indeed, this epitope is immunogenic enough to supplant the Gag immunodominant HLA-A*02 restricted epitope, SLYNTVATL. It has also been shown how a HLA-B*15 restricted CTL epitope, KMIGGIGGF of PR is attenuated by a saquinavir related mutation in drug exposed patients and is normally not found in HIV sequences obtained from drug na?��ve HLA-B*15+ patients. The role of CTL responses is a key factor in persistent low-level viremia in patients undergoing antiretroviral therapy where drug resistance has accumulated. The varying nature of peptide binding motives for the vast amounts of HLA allotypes, makes the experimental detection of HLA allotype specific CTL epitopes a laborious process. With the increase in computational power and availability of data, computational methods applied in immunological studies have become possible.