Baseline Darunavir Sensitivity Does Not Predict Response to Boosted Ritonavir plus Enfuvirtide in Triple-class-experienced Patients: BLQ Study Final Results

Prior studies have suggested that baseline phenotypic resistance to darunavir (Prezista), or fold change in sensitivity, may predict virological response in antiretroviral-experienced patients treated with ritonavir-boosted darunavir plus enfuvirtide (Fuzeon, T-20).

The present analysis, presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this week in Chicago, assessed the impact of baseline darunavir fold change and other variables on virological response to regimens containing darunavir/ritonavir plus enfuvirtide.

In this prospective, 24-week, open-label, safety and efficacy study, 142 highly treatment-experienced patients received 90 mg twice-daily enfuvirtide plus 600/100 mg twice-daily darunavir/ritonavir with optimized background treatment. Participants had previously taken NRTIs, NNRTIs, and protease inhibitors, but not enfuvirtide.

Of 142 patients enrolled, 140 were included in the safety population and 131 were included in the intention-to-treat (ITT) population (> 1 post-baseline assessment). 11 patients were excluded from the analysis due to missed post-baseline assessments. At baseline, the mean HIV RNA level was 4.69 log copies/mL and the mean CD4 cell count was 162 cells/mm3.

Logistic regression methods were used to assess the relationship of baseline darunavir fold change, genotypic sensitivity score, and CD4 count to Week 24 virological response. Darunavir fold change was defined using standard EC50 scores (50% of the maximum effective drug concentration).

Results

• 4 patients withdrew prematurely for safety reasons (1 non-treatment-related death; 2 adverse event or disease related; 1 due to enfuvirtide injection site reactions).

• At Week 24, in an ITT analysis (n = 131), 60.3% of the patients achieved a viral load below 50 copies/mL and 72.5% had a viral load below 400 copies/mL.

• Among those with a darunavir fold change < 10 (n = 88), the corresponding percentages were 63.6% below 50 copies/mL and 78.4% below 400 copies/mL.

• Among those with a darunavir fold change ? 10 but ? 40 (n = 19), the corresponding percentages were 57.9% and 84.2%.

• Among those with a darunavir fold change > 40 (n = 8), the corresponding percentages were 62.5% and 75.0%.

• Logistic stepwise regression analysis showed that patients with a CD4 count ? 100 cells/mm3 were more likely to achieve a viral load below 50 copies/mL (P = 0.020) or below 400 c/mL (P = 0.015) relative to those with lower CD4 counts.

Conclusion

Based on these findings, the researchers concluded, "The use of darunavir/ritonavir with enfuvirtide and optimized background therapy in highly antiretroviral-experienced patients naive to these two drugs resulted in high levels of virologic responses that appear to persist even in those pts with baseline darunavir fold change > 40."

Orlando Immunology Ctr., Orlando, FL; AIDS Health Care Foundation, Los Angeles, CA; Synergy Hematology Oncology, Los Angeles, CA; Therapeutic Concepts, Houston, TX; Roche Laboratories, Nutley, NJ; Stanford University, Stanford, CA.

09/18/07

Reference
E DeJesus, C Farthing, M Gottlieb and others. Response to Darunavir/Ritonavir (DRV/r) Combined with Enfuvirtide (ENF)-containing ARV in Triple-Class Experienced Patients was not Predicted by Baseline DRV Sensitivity: The BLQ Study Final Results. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, September 17-20, 2007. Abstract H-367.