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HIV Drug Therapy: Once-daily Dolutegravir Superior to Darunavir at 96 Weeks

Treatment with a triple antiretroviral combination containing the once-daily integrase inhibitor dolutegravir (Tivicay) is superior to the ritonavir-boosted protease inhibitor darunavir (Prezista) over 96 weeks of follow-up, Jean-Michel Molina of the Hôpital Saint Louis, Paris, reported this month at the HIV Drug Therapy Glasgow conference.

[Produced in collaboration with Aidsmap.com]

Dolutegravir is also a component of the fixed-dose 3-drug combination Triumeq, which also contains abacavir and lamivudine.

The findings came from the FLAMINGO (ING 114915) study, a multicenter Phase 3b trial that compared dolutegravir to darunavir/ritonavir as part of a first antiretroviral combination.

The study recruited adults living with HIV who had a viral load over 1000 copies/mL, had not taken treatment before, and showed no sign of viral resistance. The study participants were randomized to receive dolutegravir or darunavir/ritonavir with an investigator-selected nucleoside/nucleotide (NRTI) backbone regimen: tenofovir/emtricitabine (Truvada) or abacavir/lamivudine (Epzicom). Participants were stratified by baseline viral load above or below 100,000 copies/mL and by backbone regimen.

The doses administered were 50 mg dolutegravir once daily or darunavir/ritonavir 800/100 mg once daily. The primary endpoint was the proportion of people with a viral load of less than 50 copies/mL at week 48 of treatment, and the secondary endpoints were antiviral activity, safety, tolerability, health outcomes, and viral resistance.

A total of 484 people were randomized and treated, with 242 in each of the 2 treatment groups. As reported in The Lancet in April, 90% of participants receiving dolutegravir and 83% of those receiving darunavir/ritonavir achieved a viral load of less than 50 copies/mL at 48 weeks. The difference between the 2 groups being significant, investigators concluded that dolutegravir was superior to darunavir/ritonavir in treatment-naive patients.

The 96-week results from FLAMINGO were presented at the Glasgow congress. 86% of participants in the dolutegravir arm and 79% of participants in the darunavir/ritonavir arm completed the 96-week study. At week 96, the proportion of these remaining patients with a viral load of less than 50 copies/mL was 80% in the dolutegravir arm and 68% in the darunavir/ritonavir arm. Overall, virological non-response to treatment (dolutegravir 8%; darunavir/ritonavir 12%) and non-response due to other reasons (dolutegravir 12%; darunavir/ritonavir 21%) occurred less frequently with dolutegravir.

Similarly to the week 48 results, the difference between arms was most pronounced in participants with high baseline viral load (>100,000 copies/mL) (82% vs 52% response through week 96) and in people taking the tenofovir/emtricitabine backbone (79% vs 64%).  

Responses were consistent in the abacavir/lamivudine stratum. A total of 6 participants (dolutegravir 2, but none post-week 48; darunavir/ritonavir 4, including 2 post-week 48) experienced virological failure, defined in the protocol as a viral load over 200 copies/mL at or after week 24. However, none had treatment-emergent resistance to the study drugs.

As in the week 48 results, the most frequent drug-related adverse events were diarrhea, nausea, and headache, with diarrhea more common on darunavir/ritonavir (24%) than on dolutegravir (10%). Also, there were significantly more people with grade 2 fasting LDL cholesterol elevations on darunavir/ritonavir (22%) than on dolutegravir (7%). Creatinine levels for dolutegravir, higher than for darunavir/ritonavir as observed since week 2, remained stable through week 96.

In conclusion, at 96 weeks, 50 mg dolutegravir once a day remained superior to 800/100 mg darunavir/ritonavir once a day and maintained a good safety profile. Investigators concluded that 50 mg dolutegravir once a day with either abacavir/lamivudine or tenofovir/emtricitabine is a suitable option for treatment-naive patients, a conclusion endorsed in the 2014 update of the European AIDS Clinical Society (EACS) antiretroviral treatment guidelines.

FLAMINGO is ongoing in an open-label extension to provide more long-term data from people taking dolutegravir.

11/14/14

Reference

J-M Molina, B Clotet, J van Lunzen, et al. Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in treatment-naive HIV-1-infected individuals: 96-week results from FLAMINGO (ING114915). HIV Drug Therapy 2014. Glasgow, November 2-6, 2014. Abstract O153.