Rapid decline in detectability of HIV-1 drug resistance mutations
after stopping therapy (after 2 weeks)JOURNAL: AIDS
VOLUME: 13
ISSUE: 18
PAGES: 123-127
RECEIVED: 8 May 1999
ACCEPTED: 14 October 1999.
AUTHOR: Helen L. Devereux*, Mike YouleÜ, Margaret A. JohnsonÜ, Clive
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 ñ 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 ñ 9 mutations). The patients were divided into three groups: <2 weeks after stopping therapy, median 1.1 weeks (n = 8, group A); 2 weeks ñ 2 months, median 6.4 weeks (n = 7, group B) and 2 months ñ 6 months, median 12.9 weeks (n = 10, group C). Of primary mutations (protease: 30N, 46I/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. AIDS 1999, 13:123-127 © 1999 Lippincott Williams & Wilkins