Rapid decline in detectability of HIV-1 drug resistance mutations after stopping therapy

H L Devereux1, M Youle, M A Johnson

  • 1Department of Retrovirology, Royal Free and University College Medical School, London, UK.

AIDS (London, England)
|January 12, 2000
PubMed
Abstract

Insights

Drug resistant HIV-1 mutations decline rapidly after stopping combination therapy. Resistance testing is most reliable while on therapy or within two weeks of cessation for guiding future treatment decisions.

Area of Science:

  • Virology
  • Infectious Diseases
  • Pharmacogenomics

Background:

  • Antiretroviral therapy (ART) is crucial for managing HIV-1 infection.
  • Drug resistance mutations can emerge during ART, complicating treatment options.
  • Understanding the persistence and decline of these mutations after therapy cessation is vital for treatment strategy.

Purpose of the Study:

  • To determine the rate at which drug-resistant mutations in HIV-1 decline after stopping combination antiretroviral therapy.
  • To assess the impact of time off therapy on the detectability of genotypic resistance profiles.

Main Methods:

  • Genotypic resistance testing using automated DNA sequencing was performed on samples from 25 patients on multi-drug ART.
  • Samples were collected at various time points (6-175 days) after cessation of therapy.
  • Primary and secondary drug resistance mutations in protease and reverse transcriptase genes were analyzed.

Main Results:

  • All patients on therapy exhibited drug resistance mutations (1-9 mutations per patient).
  • Primary mutations persisted in 100% of patients within 2 weeks of stopping therapy, decreasing to 68% at 2 months and 15% by 6 months.
  • Secondary mutations showed a similar decline, with 98% persistence at 2 weeks, 99% at 2 months, and 57% at 6 months.

Conclusions:

  • A significant decline in detectable primary HIV-1 drug resistance mutations occurs within 13 weeks of stopping combination therapy.
  • HIV-1 resistance testing for guiding future therapy decisions is most reliable when conducted during existing therapy or within two weeks of its discontinuation.

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