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

Abstract

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, 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.