Long-term persistence of primary genotypic resistance after HIV-1 seroconversion

David Pao1, Ushan Andrady, Janette Clarke

  • 1Royal Sussex County Hospital, Brighton, United Kingdom.

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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