Background: Darunavir/ritonavir (DRV/r) is the most widely recommended protease inhibitor in treatment guidelines. The approved dose of DRV/r is 800/100 mg once daily (QD) for patients with no PI resistance. In the POWER studies, patients treated with a lower dose - 400/100mg QD - showed similar reductions in HIV RNA to the standard dose, with consistent results shown in other pilot studies (DARULIGHT, DRV600). Reductions in the dose of DRV/r could improve safety and lower costs of mass treatment in low- and middle-income countries. Low cost generic DRV/r is becoming available in many countries as patents expire.
Methods: In this study in Johannesburg, South Africa, 300 patients previously stable on 2NRTI+LPV/r with HIV RNA < 50 copies/mL were randomised to 2NRTI+DRV/r 400/100 mg QD (n=148) or continued 2NRTI+LPV/r (n=152). Treatment success was defined as HIV RNA < 50 copies/mL at Week 48 (FDA snapshot). Treatment arms were compared using the new FDA non-inferiority (NI) margin of -4% for switch studies, using the Intent to Treat (ITT) population.
Results: Patients were 68% female and 99.7% Black, with mean age 42 years, CD4 count 621 cells/µL, body weight 72 kg. In the primary efficacy analysis, HIV RNA < 50 copies/mL by Week 48 (ITT) was 143/148 (96.7%) in the DRV/r arm versus 145/152 (95.4%) in the LPV/r arm (Difference = +1.2% (95% CI = -3.7% to +6.2%). Of the 12 patients with failure, 7 had low-level viraemia (50-199 copies/mL), 2 had transient high-level viraemia at Week 48 which resolved after adherence counselling; 3 had missing data. Summary safety data is shown in the table below.
Conclusions: In this study for patients with HIV RNA < 50 copies/mL at baseline, switching to 2NRTI+DRV/r 400/100 mg once daily showed non-inferior efficacy versus 2NRTI+LPV/r in the primary efficacy analysis (96% versus 95%), within the -4% FDA non-inferiority margin for switch studies. For stable patients, switching from LPV/r to DRV/r 400/100 QD would improve convenience and could lower long-term costs. New clinical trials are required to evaluate DRV/r 400/100 mg after first-line treatment failure, where this PI is most widely used.