Rapid decline in detectability of HIV-1 drug resistance mutations after stopping therapy.
OBJECTIVE
To investigate the rate of decline of drug resistant viruses after stopping therapy.


METHODS
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.
Devereux
H L
HL
Department of Retrovirology, Royal Free and University College Medical School, London, UK.
Youle
M
M
Johnson
M A
MA
Loveday
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000821:virology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004359:Drug Therapy, Combination; D016333:HIV Protease / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D016879:Salvage Therapy; D018709:Statistics, Nonparametric
D019380:Anti-HIV Agents; D012194:RNA-Directed DNA Polymerase; D016333:HIV Protease