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As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
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Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
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Published on: April 9, 2014

Nonpolymorphic human immunodeficiency virus type 1 protease and reverse transcriptase treatment-selected mutations.

Rajin Shahriar1, Soo-Yon Rhee, Tommy F Liu

  • 1Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA.

Antimicrobial Agents and Chemotherapy
|September 2, 2009
PubMed
Summary

Antiretroviral drug resistance in human immunodeficiency virus type 1 (HIV-1) involves protease and reverse transcriptase (RT) mutations. This study reveals an increasing prevalence of these drug-selected mutations in HIV patients undergoing treatment.

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Area of Science:

  • Virology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Antiretroviral (ARV) drug resistance in human immunodeficiency virus type 1 (HIV-1) is a growing concern.
  • The spectrum of mutations in HIV-1 protease and reverse transcriptase (RT) selected by ARV drugs requires continuous monitoring due to evolving treatment patterns and increasing sequence data from diverse viral subtypes.

Purpose of the Study:

  • To compare the prevalence of protease and RT mutations in HIV-1 group M sequences between individuals with and without a history of protease inhibitor (PI) or RT inhibitor (RTI) treatment.
  • To identify nonpolymorphic mutations under ARV selection pressure and assess changes in their prevalence over time and across different viral subtypes.

Main Methods:

  • Analysis of protease sequences from 26,888 individuals and RT sequences from 25,695 individuals.
  • Classification of mutations based on their prevalence in untreated individuals and whether their prevalence increased fivefold with ARV therapy.
  • Comparison of mutation prevalence with previous studies, noting increases in sample size and inclusion of non-subtype B viruses.

Main Results:

  • Identified 88 PI-selected and 122 RTI-selected nonpolymorphic mutations with a fivefold higher prevalence in ARV-treated individuals compared to ARV-naïve individuals.
  • Observed a 47% increase in PI-selected mutations and a 77% increase in RTI-selected mutations compared to a 2005 study.
  • Demonstrated a significant increase in the number of identified mutations with a larger dataset and broader subtype representation.

Conclusions:

  • Many nonpolymorphic mutations in HIV-1 protease and RT are under selection pressure from ARV drugs.
  • The landscape of treatment-selected mutations is dynamic, influenced by evolving treatment regimens, increased patient data, and greater availability of sequences from non-subtype B viruses.