Drug Resistance Mutations during Structured Treatment Interruptions

Abstract

Background

We assessed whether treatment interruptions induce selection of mutations associated with drug resistance in the Swiss–Spanish Intermittent Treatment Trial (SSITT). Patients had been on HAART without previous failure and had undetectable viraemia for at least 6 months. Their HAART was interrupted for 2 weeks and restarted for 8 weeks. After four of these cycles, treatment was definitively interrupted at week 40.

Methods

Genotypic resistance testing was performed in 87/97 Swiss patients: in those failing treatment before week 40, at the time of first viral rebound >500 copies/ml off treatment and preceding failure to reach RNA <50 copies/ml after 8 weeks of re-treatment; for patients without virological failure, on the first sample with HIV-1 RNA >1000 copies/ml after week 40.

Results

Mutations associated with drug resistance were detected in 9/25 (36%) patients with virological failure during the first 40 weeks and in 6/59 (10%) patients after week 40. Overall, drug resistance mutations were detected in 17% of patients, all but two with the 184V/I mutation. Among the 74 patients receiving lamivudine, the M184V/I mutation was detected in 13/74 (17.6%) patients. A wild-type codon at position 184 was detected in previous samples in all b'ut two. The relative risk for virological failure was 2.55-fold higher in patients with the M184V/I mutation than in patients without detectable mutation (P=0.007).

Conclusions

The M184V/I mutation is frequently selected during repeated treatment interruptions.