In well-suppressed, treatment-experienced adults with HIV, decreasing the dose of ritonavir-boosted darunavir (darunavir/r) from the standard dose is associated with a high rate of virologic suppression and was found to be safe over a 48-week period, according to researchers led by Jean-Michel Molina at the department of infectious diseases, Saint-Louis Hospital, AP-HP, Paris and the University of Paris Diderot, Sorbonne Paris University, Paris.
Once-daily darunavir/r at a dose of 800 mg/100 mg is effective for both treatment-naive individuals and those who have used other therapies but who do not harbour darunavir resistance-associated mutations (RAMs). It also has a better tolerability profile than ritonavir-boosted atazanavir. In this study, the authors investigated the use of a lower dose of darunavir (400 mg) in combination with ritonavir in well-suppressed patients who are currently being treated with a standard dose of once-daily darunavir/r plus 2 nucleoside reverse transcriptase inhibitors (NRTIs).
The cohort included 100 HIV-1-infected adults without darunavir or NRTI RAMs and a plasma HIV RNA level 50 copies/mL who received once-daily darunavir/r (800/100 mg) for 12 or more months and 2 NRTIs for 6 or more months, and their regimen was then changed to darunavir/r 400 mg/100 mg with the same NRTIs.
At week 48, 87 out of 95 patients (5 were excluded from the analysis) maintained a plasma HIV RNA level <50 copies/mL, and the success rate of reduced-dose therapy was 91.6% (95% CI, 84.1%-96.3%). A moderate increase in median CD4 cell count of 40 cells/mm3 was noted from baseline to week 48 (P= 0.049).
A randomised trial evaluating reduced-dose darunavir is currently ongoing, and “should this trial confirm our findings, this strategy could lead to significant savings for second-line therapy in low- and middle-income countries,” wrote the authors.
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.
Jean-Michel Molina, Sebastien Gallien, Marie-Laure Chaix, El Mountacer El Abbassi, Isabelle Madelaine, Christine Katlama, Nadia Valin, Pierre Delobel, Kristell Desseaux, Gilles Peytavin, Juliette Saillard, François Raffi, Sylvie Chevret