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Updated: Aug 14, 2026

An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings
Published on: March 30, 2014
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.
Objective:
To investigate the rate of decline of drug resistant viruses after stopping therapy.
Design:
Twenty-five patients receiving multiple combination therapies (mean five; range three to nine drugs) for more than 3 months were tested for HIV-1 resistance on therapy and off therapy. The sample off therapy was tested 6-175 days after stopping therapy.
Methods:
Patients were tested for genotypic changes associated with drug resistance using an in-house automated DNA sequencing assay to detect resistance in the protease and reverse transcriptase genes.
Results:
All samples tested when patients were on therapy showed evidence of drug resistance (range 1-9 mutations). The patients were divided into three groups: <2 weeks after stopping therapy, median 1.1 weeks (n = 8, group A); 2 weeks-2 months, median 6.4 weeks (n = 7, group B) and 2 months-6 months, median 12.9 weeks (n = 10, group C). Of primary mutations (protease: 30N, 461/L, 82A, 90M; reverse transcriptase: 70R, 184I/V, 215 Y/F) detected on therapy 100% remained after stopping therapy in group A; 68% remained in group B and 15% remained in group C. For secondary mutations 98% remained in group A; 99% remained in group B and 57% in group C.
Conclusions:
This study showed a rapid decline in detectability of the majority of primary mutations within 13 weeks of stopping combination therapy. From this data, HIV-1 resistance testing to direct patients' therapy should only be carried out when on existing therapy, or < 2 weeks off therapy, if reliable decisions are to be made relating to future combinations.
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.
Related Concept Videos
Retrovirus Life Cycles
Viral Mutations
Therapeutic Drug Monitoring: Affecting Factors
Inhibitors of Virion Maturation and Assembly

