Darunavir in patients who failed on fos-amprenavir: efficacy at week 48

Background

Darunavir and fos-amprenavir share similar in vitro suceptibility patterns. Whether previous failure with fos-amprenavir leads to impaired response to darunavir remains an open question.

Methods

We evaluated week 48 response to a darunavir-containing regimen in patients who previously failed on fos-amprenavir.

Summary of results

17 patients (pts) fulfilling the selection criteria were retrieved from our database. They had been exposed to a median of six NRTIs, one NNRTI and seven PIs (five pts being tipranavir experienced). Median baseline plasma HIV-RNA was 5,775 copies/ml and median CD4 count was 200 cells/mm³. Median number of IAS protease mutations was 11 (IQR 9–12), median number of darunavir mutations was one (range 0–4). 14/17 p (82%) were genotypically resistant to fos-amprenavir. The new regimen included enfuvirtide (16 pts), etravirine (10 pts), raltegravir (four pts) and maraviroc (two pts).

At week 48, VL below 50 copies/ml was obtained in 9/17 pts (53%). Among the eight pts who failed on darunavir, seven had no major mutation for darunavir at baseline, the remaining pt had one major mutation. No correlation was found between virological response at week 48 and baseline characteristics such as number of mutations for fos-amprenavir, treatment history, and other ARV drugs in the new regimens. Of note, enfuvirtide was used for the first time in 6/9 responding pts vs. 3/8 in the failing pts.

Conclusion

Our data suggest that prior failure on fos-amprenavir has limited impact on response to darunavir and that fos-amprenavir selected key mutations have low impact on DRV virological response