Reduced dose darunavir safe and effective in viral suppression

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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.

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.

Authors
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

Infectious Disease Advisor material
Journal of Antimicrobial Chemotherapy abstract


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