Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Oct;25(5):316-28.
doi: 10.1007/s12250-010-3122-4. Epub 2010 Oct 8.

Indinavir resistance evolution in one human immunodeficiency virus type 1 infected patient revealed by single-genome amplification

Qing-Mao Geng  1 , Han-Ping Li, Zuo-Yi Bao, Yong-Jian Liu, Dao-Min Zhuang, Lin Li, Si-Yang Liu, Jing-Yun Li
Affiliations

Indinavir resistance evolution in one human immunodeficiency virus type 1 infected patient revealed by single-genome amplification

Qing-Mao Geng et al. Virol Sin. 2010 Oct.

Abstract

Human Immunodeficiency Virus Type 1 exists in vivo as quasispecies, and one of the genome's characteristics is its diversity. During the antiretroviral therapy, drug resistance is the main obstacle to effective viral prevention. Understanding the molecular evolution process is fundamental to analyze the mechanism of drug resistance and develop a strategy to minimize resistance.

Objective: The molecular evolution of drug resistance of one patient who had received reverse transcriptase inhibitors for a long time and had treatment which replaced Nevirapine with Indinavir was analyzed, with the aim of observing the drug resistance evolution pathway.

Methods: The patient, XLF, was followed-up for six successive times. The viral populations were amplified and sequenced by single-genome amplification. All the sequences were submitted to the Stanford HIV Drug Resistance Database for the analysis of genotypic drug resistance.

Results: 149 entire protease and 171 entire reverse transcriptase sequences were obtained from these samples, and all sequences were identified as subtype B. Before the patient received Indinavir, the viral population only had some polymorphisms in the protease sequences. After the patient began Indinavir treatment, the variants carrying polymorphisms declined while variants carrying the secondary mutation G73S gained the advantage. As therapy was prolonged, G73S was combined with M46I/L90M to form a resistance pattern M46I/G73S/L90M, which then became the dominant population. 97.9% of variants had the M46I/G73S/L90M pattern at XLF6. During the emergence of protease inhibitors resistance, reverse transcriptase inhibitors resistance maintained high levels.

Conclusion: Indinavir-resistance evolution was observed by single-genome amplification. During the course of changing the regimen to incorporate Indinavir, the G73S mutation occurred and was combined with M46I/L90M.

PubMed Disclaimer

Comment in

  • Indinavir resistance evolution: a comment.
    Wiwanitkit V. Wiwanitkit V. Virol Sin. 2011 Feb;26(1):72. doi: 10.1007/s12250-011-3173-6. Epub 2011 Feb 18. Virol Sin. 2011. PMID: 21331894 Free PMC article. No abstract available.

References

    1. Alexander D. C. A rapid method for determining clone frequency in complex populations using PCR and the Poisson distribution. Nucl Acids Res. 1990;18(24):7453–7454. doi: 10.1093/nar/18.24.7453. - DOI - PMC - PubMed
    1. Bélec L., Piketty C., Si-Mohamed A., et al. High levels of drug-resistant Human Immunodeficiency Virus variants in patients exhibiting increasing CD4+ T cell counts despite virologic failure of protease inhibitor-containing antiretroviral combination therapy. J Infect Dis. 2000;181(5):1808–1812. doi: 10.1086/315429. - DOI - PubMed
    1. Chen Z., Li Y., Schock H. B., et al. Three-dimensional structure of a mutant HIV-1 protease displaying cross-resistance to all protease inhibitors in clinical trials. J Biol Chem. 1995;270(37):21433–21436. doi: 10.1074/jbc.270.37.21942. - DOI - PubMed
    1. Clavel F., Hance A. J. HIV drug resistance. N Engl J Med. 2004;350(10):1023–1035. - PubMed
    1. Coffin J. M. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995;267:483–489. doi: 10.1126/science.7824947. - DOI - PubMed

Publication types

MeSH terms

Substances