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अमूर्त

Genetic Mutations Affecting the Success and Failure of HIV Regimens

George Towfic, Judy Munshower, Samira Kettoola, Fadi Towfic, Frank Graziano, John Viner and Helena Tsotsis

Recently, genotypic testing (the identification of viral mutations and their associated drug resistance) has be- come a popular procedure to identify drug resistanc e before advising alternative therapy regimens.

Since major drug resistance factors are associated with the frequency of viral mutations, many researchers have explored HIV’s mutation frequency at specified nucl e- otide sequence positions in response to different t ypes of drug therapy. However, only a handful of papers dis- cuss major genetic signatures that lead to positive pa- tients’ responses to a specific type of drug therap y.

Using existing clinical drug resistance libraries, we were able to determine the most common mutations in the HIV protease (PR) enzymes associated with the s uc- cess and failure of Protease Inhibitor (PI) HIV/AID S drug regimens. A total of 2,079 patient records sel ected from the Stanford HIV drug resistance database has been considered in identifying genetic sequences associa ted with positive responses to PR-inhibitors drug regim ens. We show that patients who responded positively to P ro- tease Inhibitor therapy have consistently maintaine d specific nucleic acids bases at specific positions of their HIV nucleotide sequences. When virus sequences ob- tained from groups of patients who did not respond well to PI therapy were compared against virus sequences at the same positions from patients who did respond we ll, we noticed that the two patient groups differ at th ese positions.