Stable patients on a twice-daily lopinavir/ritonavir (LPV/r)-based second-line regimen who switched to a once-daily 400/100 mg darunavir/ritonavir (DRV/r) one maintained similar virological suppression to those who remained on LPV/r at 48 weeks. [1] These data from Johannesburg were presented by researchers at the University of Witwatersrand, WITS Reproductive Health and HIV Institute, Imperial College London and Liverpool University at AIDS 2018.
The approved dose of DRV/r is 800/100 mg once daily for people with no PI resistance. [2] DRV/r is rarely used in sub-Saharan Africa because of its high cost. DRV/r is considered to be a good candidate for dose optimisation. [2]
In this study, 300 participants, stable on 2 NRTI + LPV/r with viral load < 50 copies/mL, were randomised to 2 NRTI + DRV/r 400/100 mg once daily (n=148) or to continue on their LPV/r-based regimen (n=152).
The study defined treatment success as viral load <50 copies/mL at week 48 (FDA snapshot). Treatment arms were compared using the new US Food and Drug Administration (FDA) non-inferiority margin for switch studies of -4%, using the Intent to Treat (ITT) population. At baseline participants were 68% female and 99.7% black, with median of age 42 years, and CD4 count >600 cells/mm3.
In the primary efficacy analysis, viral load < 50 copies/mL by week 48 was 95.3% in the DRV/r arm versus 93.4% in the LPV/r arm. Difference +1.9% (95% CI: -3.7% to +6.5). DRV/r at the lower dose of 400/100 mg once daily showed non-inferior efficacy to LPV/r in this switch study.
These results support further studies with low dose DRV/r, including in PI-naive second-line patients. Optimised DRV/r 400/100 mg could be cheaper to produce than LPV/r and atazanavir/r.
Abstract
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.
Authors
F Venter, M Moorhouse, S Sokhela, E Maharaj, G Akpomiemie, B Simmons, C Serenata, A Hill
[link url="http://i-base.info/htb/34677"]i-base material[/link]
[link url="http://programme.aids2018.org/Abstract/Abstract/13192"]AIDS 2018 abstract[/link]