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Amplification of Near Full-length HIV-1 Proviruses for Next-Generation Sequencing
Published on: October 16, 2018
Long-term persistence of primary genotypic resistance after HIV-1 seroconversion
David Pao1, Ushan Andrady, Janette Clarke
1Royal Sussex County Hospital, Brighton, United Kingdom.
Abstract:
Primary infection with drug-resistant HIV-1 is well documented. We have followed up patients infected with such viruses to determine the stability of resistance-associated mutations. Fourteen patients who experienced primary infection with genotypic evidence of resistance were followed for up to 3 years. Drug resistance-associated mutations persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. Multidrug resistance in 2 patients was found to be stable for up to 18 months, the maximum period studied. We conclude that certain resistance-associated mutations are highly stable and these data support the recommendation that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.
Insights
Drug-resistant HIV-1 mutations are often stable long-term. Genotyping is recommended for all new HIV diagnoses to identify persistent resistance mutations.
Area of Science:
- Virology
- Infectious Diseases
- Molecular Biology
Background:
- Primary infection with drug-resistant Human Immunodeficiency Virus type 1 (HIV-1) is a growing concern.
- Understanding the long-term stability of resistance-associated mutations (RAMs) is crucial for effective treatment strategies.
Purpose of the Study:
- To determine the persistence and reversion patterns of drug resistance mutations in patients with primary HIV-1 infection.
- To evaluate the stability of specific reverse transcriptase (RT) mutations and multidrug resistance over time.
Main Methods:
- Longitudinal follow-up of 14 patients with primary HIV-1 infection and genotypic evidence of drug resistance.
- Monitoring of resistance-associated mutations in reverse transcriptase (RT) over a period of up to 3 years.
- Analysis of mutation reversion to wild-type virus and stability of multidrug resistance.
Main Results:
- Most drug resistance-associated mutations (RAMs) persisted over time in patients studied.
- Specific mutations like M41L, T69N, K103N, and T215 variants in RT showed little reversion.
- Mutations Y181C and K219Q in RT, when occurring alone, disappeared within 25 and 9 months, respectively.
- Multidrug resistance remained stable for up to 18 months in two patients.
Conclusions:
- Certain HIV-1 drug resistance mutations exhibit high stability over extended periods.
- These findings support routine HIV genotyping for all new diagnoses in areas with potential primary drug resistance.
- Early identification of stable resistance mutations can inform treatment decisions and improve patient outcomes.
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