Recent findings demonstrated that dual therapy with darunavir/ritonavir and lamivudine was non-inferior to triple therapy with darunavir/ritonavir plus tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine for the maintenance of HIV-1 viral suppression.
“Darunavir-boosted with ritonavir or cobicistat is the preferred protease inhibitor in most international guidelines of HIV therapy due to its efficacy and safety profile,” Dr Federico Pulido, from the Hospital Universitario Doce de Octubre in Madrid, Spain, and colleagues wrote. “There are no clinical trial data about the efficacy of dual therapy with boosted darunavir and lamivudine.”
Researchers examined whether dual therapy with darunavir/ritonavir and lamivudine was non-inferior to triple therapy with darunavir/ritonavir plus tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine for viral suppression of HIV. They randomly assigned 257 patients on triple therapy to either continue their treatment regimen or switch to darunavir/ritonavir and lamivudine to determine how many patients without resistance had HIV-RNA less than 50 copies/mL after 48 weeks of follow-up.
Their analysis showed that 112 of 126 participants (88.9%) who received dual therapy and 114 of 123 (92.7%) participants who received triple therapy had HIV-RNA less than 50 copies/mL (difference –3.8% [95% CI, –11 to 3.4]) at week 48. Changing to dual therapy was linked to significant increases in low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol, and minor improvement in estimated creatinine clearance. However, dual therapy was not associated with a notable increase in the total/HDL-cholesterol ratio compared with triple therapy.
Virological failure occurred in four patients receiving dual therapy and two patients receiving triple therapy. The proportion of patients in dual vs. triple therapy who experienced serious adverse events and those who discontinued treatment because of these events was 4.8% vs. 4.9% and 0.8% vs. 1.6%, respectively. These differences were not statistically significant.
“The results … indicate that the combination of darunavir/ritonavir and lamivudine is as efficacious as triple therapy with darunavir/ritonavir and two nucleos(t)ides for maintenance of virological suppression in HIV-infected participants without resistance to darunavir or lamivudine,” Pulido and colleagues wrote. “This strategy has the benefit of using darunavir – a boosted protease inhibitor with a good efficacy and safety profile – and lamivudine, a nucleoside with an excellent long-term safety profile.
Background: Our objective was to assess the therapeutic non-inferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine for maintenance of HIV-1 viral suppression.
Methods: 48-week, multicenter, open-label, non-inferiority trial (margin 12%). Patients with HIV-1 RNA <50 copies/mL for ≥6 months on triple therapy with darunavir/ritonavir and two nucleos(t)ides (tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine), with no resistance, were randomized to continue therapy (n=128) or switch to darunavir/ritonavir and lamivudine (n=129). Primary endpoint was proportion of participants with HIV-RNA <50 copies/mL after 48 weeks of follow-up according to the FDA snapshot algorithm. ClinicalTrials.gov number NCT02159599
Results: 249 received study drugs (ITT-exposed). At week 48, proportion of participants with HIV-RNA <50 copies/mL in the dual and triple therapy arms was respectively 88.9% (112/126) vs. 92.7% (114/123) [difference -3.8% (95%CI: -11.0 to 3.4)]. Four participants in the dual therapy arm and two in the triple therapy arm developed protocol defined virological failure. Switching to dual therapy was associated with a significant increase in total, LDL and HDL cholesterol, but not in the total/HDL-cholesterol ratio, and a non-significant improvement in estimated creatinine clearance. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% (6/126) vs. 4.9% (6/123; p=0.97) and in 0.8% (1/126) vs 1.6% (2/123; p=0.55) in dual therapy vs. triple therapy, respectively.
Conclusions: Dual therapy with darunavir/ritonavir and lamivudine demonstrated non-inferior therapeutic efficacy and similar tolerability compared to triple therapy.
Federico Pulido, Esteban Ribera, María Lagarde, Ignacio Pérez-Valero, Rosario Palacios, José A Iribarren, Antoni Payeras, Pere Domingo, José Sanz, Miguel Cervero, Adrián Curran, Francisco J Rodríguez-Gómez, María J Téllez, Pablo Ryan, Pilar Barrufet, Hernando Knobel, Antonio Rivero, Belén Alejos, María Yllescas, José R Arribas