Abstract

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.

Highlights

  • IntroductionReceived June 27, 2009; Accepted September 01, 2009; Published September 01, 2009

  • Received June 27, 2009; Accepted September 01, 2009; Published September 01, 2009Major factors that determine the success of Human Immunodeficiency Virus (HIV) therapy include the measurement and monitoring of Cluster of Differentiation 4 (CD4) counts, Ribonucleic Acid (RNA) levels, and the determination of the type of viral sequences and drug resistance mutations

  • Out of 2,079 records stored in the Stanford PR database, we found 189 patient IDs with monotonically non-decreasing CD4 counts and increasing RNA levels throughout their clinical trial history

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Summary

Introduction

Received June 27, 2009; Accepted September 01, 2009; Published September 01, 2009. Major factors that determine the success of HIV therapy include the measurement and monitoring of CD4 counts, RNA (ribonucleic) levels, and the determination of the type of viral sequences and drug resistance mutations. The HIV-1 virus attaches to CD4 with a particular protein in its viral. Volume 2(9) : 372-379 (2009) - 372 ISSN:0974-276X JPB, an open access journal pyrosequencing of individual DNA molecules (Ronaghi et al, 1996; Nyrén, 2007), bidirectional sequencing (Mitsuya et al, 2008) and array sequencing (Miyada et al, 2008) (which has been used for sequence detection). Since different sequencing methods have different error tolerance, we selected patients’ RNA sequences obtained using the pyrosequencing sequencing procedure (Wang et al, 2007)

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