Background:  The protease inhibitors (PI) amprenavir (APV) and darunavir (DRV) share some common genetic determinants of decreased susceptibility. Thus, it is possible that prior exposure to APV could influence the virological response to DRV/ritonavir (r)- containing regimens. Virological response was investigated in patients enrolled in the POWER 1, 2, and 3 studies receiving the recommended DRV/r dose (600/100 mg twice daily) who at screening were failing an APV-containing regimen or had unequivocal evidence of APV resistance.

Methods:  We evaluated the mean ±SE log₁₀ viral load drop (NC = F) and proportion of patients ±SE achieving <50 copies/mL of HIV-1 RNA (TLOVR) at 48 weeks in POWER 1, 2, and 3 according to the following criteria at screening:  use of APV as part of the failing regimen; any previous use of APV; use of APV as part of the failing regimen and having a predicted fold change to APV >9.8 (CCO₂ for APV/r vircoTYPE assay); having a predicted FC >9.8 to APV;  having a measured fold change >2.5 to APV (BCO for APV Antivirogram assay); or all patients irrespective of prior use or susceptibility to APV. Predicted fold-change values were determined with the virtual phenotype linear model while measured ones, with the Antivirogram assay. In addition, we determined the correlation coefficients (r) values between baseline fold change (n = 455) to DRV and all approved PI.

Results:  The highest r between fold-change values was observed for DRV and APV (0.89), followed by DRV and lopinavir (0.55), DRV and atazanavir (0.41), DRV and tipranavir (0.38), DRV and saquinavir (0.36), DRV and indinavir (0.35), and DRV and nelfinavir (0.29). The mean viral load drop among the subgroups was:  a) –1.47±0.15 log₁₀ (n = 73), b) –1.46±0.08 log₁₀ (n = 270), c) –1.43±0.16 log₁₀ (n = 66), d) –1.40 ±0.08 log₁₀ (n = 296), e) –1.61±0.07 log₁₀ (n = 379), and f) –1.65±0.06 log₁₀ (n = 450). For the same subgroups, the proportion achieving <50 copies/mL was: a) 38%±5.6% (n = 74), b) 36%±2.9% (n = 272), c) 36%±5.9% (n = 67), d) 35%±2.8% (n = 299), e) 43%±2.5% (n = 382), and f) 45%±2.3% (n = 455). The median number (inter-quartile range) of APV International AIDS Society (IAS) -USA mutations in subgroups a) and c) were 4 (4, 5) and 5 (4, 5), respectively.   

Conclusions:  Based on this stringent analysis, high levels of resistance to, and use of, APV at screening seemed to have only a minimal effect on the virological response to DRV/r 600/100 mg twice daily at 48 weeks in patients enrolled in POWER 1, 2, and 3. These findings reinforce the concept that DRV retains activity against isolates resistant to APV.