Jean-Michel Molina1,2, Sebastien Gallien3, Marie-Laure Chaix2,4, El Mountacer El Abbassi5, Isabelle Madelaine6, Christine Katlama7, Nadia Valin8, Pierre Delobel9, Kristell Desseaux2, Gilles Peytavin10, Juliette Saillard11, François Raffi12, Sylvie Chevret2,5. 1. Department of Infectious Diseases, Saint-Louis Hospital, AP-HP, Paris, France. 2. University of Paris Diderot, Sorbonne Paris University, Paris, France. 3. Department of Immunology and Infectious Diseases, Henri-Mondor Hospital, Creteil, France. 4. Laboratory of Virology, Saint-Louis Hospital, AP-HP, Paris, France. 5. Department of Biostatistics, Saint-Louis Hospital, AP-HP, Paris, France. 6. Pharmacy, Saint-Louis Hospital, AP-HP, Paris, France. 7. Department of Infectious Diseases, Pitié Salpêtrière Hospital, Paris, France. 8. Department of Infectious Diseases, Saint-Antoine Hospital, Paris, France. 9. Department of Infectious Diseases, Toulouse University Hospital, Toulouse, France. 10. Department of Pharmacology, Bichat Hospital, Paris, France. 11. ANRS, Paris, France. 12. Infectious Disease Department and INSERM CIC 1413, University Hospital of Nantes, Nantes, France.
Abstract
Objectives: To assess whether low-dose ritonavir-boosted darunavir (darunavir/r) in combination with two NRTIs could maintain virological suppression in patients on a standard regimen of darunavir/r + two NRTIs. Design: A multicentre, Phase II, non-comparative, single-arm, open-label study. Setting: Tertiary care hospitals in France. Subjects: One hundred HIV-1-infected adults with no darunavir or NRTI resistance-associated mutations (RAMs) and a plasma HIV RNA level ≤50 copies/mL for ≥12 months on once-daily darunavir/r (800/100 mg) + two NRTIs for ≥6 months were switched to darunavir/r 400/100 mg with the same NRTIs. Primary outcome measure: Proportion of patients with treatment success: plasma HIV RNA level ≤50 copies/mL up to 48 weeks without any change in the study regimen, in a modified ITT (mITT) analysis. Results: At baseline, most patients were male (78%), with a median age of 43 years, median duration of HIV RNA ≤50 copies/mL of 35 months and median CD4 T cell count of 633 cells/mm3. Seventy-six percent received tenofovir/emtricitabine and 24% abacavir/lamivudine. Five patients were excluded from the mITT analysis. The rate of treatment success through to week 48 was 91.6% (87/95; 95% CI 84.1%-96.3%). No RAM was detected in three amplifiable genotypes. A total of 212 adverse events (AEs) occurred in 64 patients (64%); 9 AEs were serious, none leading to treatment discontinuation. Conclusions: In HIV-infected patients well suppressed with darunavir/r (800/100 mg) and two NRTIs, a reduction of the darunavir dose to 400 mg/day maintained virological efficacy and was safe over 48 weeks.
Objectives: To assess whether low-dose ritonavir-boosted darunavir (darunavir/r) in combination with two NRTIs could maintain virological suppression in patients on a standard regimen of darunavir/r + two NRTIs. Design: A multicentre, Phase II, non-comparative, single-arm, open-label study. Setting: Tertiary care hospitals in France. Subjects: One hundred HIV-1-infected adults with no darunavir or NRTI resistance-associated mutations (RAMs) and a plasma HIV RNA level ≤50 copies/mL for ≥12 months on once-daily darunavir/r (800/100 mg) + two NRTIs for ≥6 months were switched to darunavir/r 400/100 mg with the same NRTIs. Primary outcome measure: Proportion of patients with treatment success: plasma HIV RNA level ≤50 copies/mL up to 48 weeks without any change in the study regimen, in a modified ITT (mITT) analysis. Results: At baseline, most patients were male (78%), with a median age of 43 years, median duration of HIV RNA ≤50 copies/mL of 35 months and median CD4 T cell count of 633 cells/mm3. Seventy-six percent received tenofovir/emtricitabine and 24% abacavir/lamivudine. Five patients were excluded from the mITT analysis. The rate of treatment success through to week 48 was 91.6% (87/95; 95% CI 84.1%-96.3%). No RAM was detected in three amplifiable genotypes. A total of 212 adverse events (AEs) occurred in 64 patients (64%); 9 AEs were serious, none leading to treatment discontinuation. Conclusions: In HIV-infectedpatients well suppressed with darunavir/r (800/100 mg) and two NRTIs, a reduction of the darunavir dose to 400 mg/day maintained virological efficacy and was safe over 48 weeks.