Simplification from twice-daily to once-daily darunavir/ritonavir in a randomized trial among HIV-infected persons with HIV-1 RNA suppression on antiretroviral therapy.

BACKGROUND: DRIVESHAFT is a randomized, open-label, 48-week clinical trial that examined virological outcomes and safety of antiretroviral simplification among virologically suppressed, treatment-experienced HIV-infected patients switching from darunavir/ritonavir (DRV/r) twice-daily-based regimens to a once-daily DRV/r component. METHODS: HIV-infected adults with a stable antiretroviral regimen including DRV/r 600/100 mg twice daily plus a minimum of two other antiretrovirals, <2 historical DRV-associated mutations and HIV RNA<40 copies/ml for at least 12 weeks prior to entry were eligible. Participants were randomized 1:1 to switch DRV/r to 800/100 mg once daily or maintain their current regimen. The primary end point was HIV-1 RNA<40 copies/ml at week 48 using the Snapshot algorithm. RESULTS: Demographics and baseline characteristics were similar between arms. Virological suppression was greater in the DRV/r once-daily (n=30) versus twice-daily (n=30) arm at week 48 (90.0% versus 83.3%; 95% CI: -11.5, 24.8). Three subjects discontinued the once-daily arm, with four discontinuations and one virological failure in the twice-daily arm. No discontinuations were related to adverse events. Reduction in LDL was significantly greater in the once-daily arm at week 24 (-8.0 mg/dl versus 3.3 mg/dl; P=0.04). There was a trend towards suboptimal adherence <90% to antiretrovirals among subjects taking twice-daily versus once-daily DRV/r by week 48 (12.0% versus 0.0%; P=0.06). CONCLUSIONS: Switching from twice-daily to once-daily DRV/r in virologically suppressed patients maintains virological control, with greater reduction in LDL cholesterol by 24 weeks. This study provides pilot data that could be used to design a non-inferiority study to definitively answer the question of whether switching from twice-daily to once-daily DRV/r maintains viral suppression. ClinicalTrials.gov number: NCT01423812.