Dolutegravir (DTG), the third integrase inhibitor approved by the FDA, previously has been compared with raltegravir and with efavirenz in antiretroviral-naive patients. At ICAAC, data from an ongoing open-label comparison of DTG with ritonavir-boosted darunavir (DRV/r) were presented.
The FLAMINGO study randomized 484 antiretroviral-naive patients to receive DTG 50 mg QD or DRV/r 800/100 mg QD in combination with 2 cofomulated nucleoside analogues selected by investigator choice (67% of patients received tenofovir/emtricitabine and 33% received abacavir/lamivudine). At baseline, 10% of study participants had a CD4 count of <200 copies/µL and 25% had HIV RNA levels of >100,000 copies/mL.
At the end of 48 weeks, using the FDA snapshot analysis, 90% of patients in the DTG arm and 83% of patients in the DRV/r arm had a HIV viral load of <50 copies/mL. A predetermined secondary analysis demonstrated superiority of DTG (p = .025). In patients with baseline HIV viral load of >100,000 copies/mL, 93% of DTG recipients and 70% of DRV/r recipients achieved a viral load of <50 copies/mL. However, virologic failure occurred at similar rates in the two arms--in 6% of the DTG group and 7% of the DRV/r group, while discontinuation owing to adverse effects or other reasons occurred more frequently in the DTG arm (4% vs 10%, respectively). There were no differences in rates of viral suppression according to patients' NRTI backbones. Increases in CD4 cell counts were 210 cells/µL in each group. Only 2 patients in each treatment arm met the criteria for resistance testing; no primary integrase, protease, or nucleoside resistance mutations were identified.
The most common adverse events in the both treatment arms included diarrhea (DTG 17%, DRV/r 29% ), nausea (DTG 16%, DRV/r 18%) and headache (DTG 15%, DRV/r 10%). In terms of lab abnormalities, the serum creatinine in DTG recipients increased 0.1-0.2 mg/dL, attributable to DTG's inhibition of renal tubular secretion of creatinine via OCT2. Increases in fasting LDL were somewhat higher in the DRV/r group. Among patients receiving DTG, 7% had a Grade 2-4 increase in creatinine kinase, compared with 4% in the DRV/r group.
Clinical Bottom Line
In summary, 90% of treatment-naive patients randomized to DTG achieved virologic suppression at week 48 compared with 83% of DRV/r patients. Both medications were well tolerated overall. Investigators proposed that the difference in overall outcomes was attributable to the higher rates of virologic response to DTG in persons with high baseline viral load and to fewer discontinuations in the DTG group. It is not clear whether the open-label protocol drove some of the differences in discontinuation.
In studies of initial ARV therapy, DGT has been compared with raltegravir and efavirenz, and now with darunavir/ritonavir. Results from all studies have demonstrated virologic efficacy rates that are comparable with each of these gold-standard agents, with comparably low rates of adverse effects, and (amazingly) no emergence of integrase resistance has been reported.