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.
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Foundation items: National Natural Science Foundation of China (30830088 and 30800938); The National Key and Special Projects on Major Infectious Disease Grant (2008 ZX10001-004)
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Geng, Qm., Li, Hp., Bao, Zy. et al. Indinavir resistance evolution in one human immunodeficiency virus type 1 infected patient revealed by single-genome amplification. Virol. Sin. 25, 316–328 (2010). https://doi.org/10.1007/s12250-010-3122-4
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DOI: https://doi.org/10.1007/s12250-010-3122-4