April 4, 2017
Combined with tenofovir alafenamide/emtricitabine (TAF/FTC, Descovy), the investigational HIV integrase inhibitor bictegravir matched the licensed integrase inhibitor dolutegravir (Tivicay, DTG) in viral suppression and safety in a double-blind phase 2 trial. Phase 3 trials of bictegravir are underway.
Three integrase inhibitors -- raltegravir (Isentress), dolutegravir and cobicistat (Tybost)-boosted elvitegravir (Vitekta) -- rank as recommended components of first-line antiretroviral regimens. Bictegravir is a potent once-daily integrase inhibitor that does not require boosting. In vitro it maintains activity against virus resistant to the licensed integrase inhibitors. Researchers at 22 U.S. outpatient clinics conducted this double-blind, placebo-controlled, phase 2 comparison of bictegravir and dolutegravir, both with TAF/FTC, in previously untreated people.
The study included antiretroviral-naive adults with a viral load above 1000 copies/mL and HIV sensitive to TAF and FTC. Participants could not have hepatitis B or C infection or an AIDS-defining condition within 30 days of screening. Researchers randomized them 2:1 to 75 mg of bictegravir once daily or 50 mg of dolutegravir once daily plus coformulated TAF/FTC.
The 65 participants randomized to bictegravir had a median age of 30 years, compared with 36 years for the 33 people randomized to dolutegravir. Overall, 57% were white and 37% black. Median pretreatment viral load stood at 4.45 log10 copies/mL (about 28,000 copies/mL), and 12% had a viral load above 100,000 copies/mL. Median pretreatment CD4 count measured 444 cells/mm3, with no significant difference between groups.
After 24 weeks, 63 of 65 people randomized to bictegravir (97%) and 31 of 33 randomized to dolutegravir (94%) had a viral load below 50 copies/mL by the FDA snapshot algorithm, the primary endpoint (weighted difference 2.9%, 95% confidence interval -8.5 to 14.2, P = .50). After 48 weeks, 97% assigned to bictegravir and 91% assigned to dolutegravir had a viral load below 50 copies/mL (P = .17). Median adherence at week 48 was 97% in the bictegravir group and 96% in the dolutegravir group, and no one stopped treatment because of loss of efficacy. No resistance mutations arose in the bictegravir group; a transient T97A integrase mutation arose in the dolutegravir group. Mean CD4 count rose by an average 258 cells/mm3 with bictegravir and 192 cells/mm3 with dolutegravir (P = .16).
Through 48 weeks, 85% in the bictegravir arm and 67% in the dolutegravir arm had a treatment-emergent adverse event, usually diarrhea (12% and 12%) or nausea (8% and 12%). One person taking bictegravir with a history of atopic dermatitis stopped study drugs after 24 weeks because of urticaria. There were no treatment-related serious adverse events in either group.
Rates of grade 2 to 4 lab abnormalities were similar in the two groups. Through 48 weeks, creatinine clearance fell 7.0 mL/min with bictegravir and 11.3 mL/min with dolutegravir. Grade 2 to 4 aminotransferase elevations were more frequent with bictegravir than dolutegravir (9% versus 3%); all resolved or improved on treatment, except in one bictegravir participant with acute hepatitis C infection and ongoing alcohol abuse.
Two double-blind phase 3 trials are comparing single-pill bictegravir/TAF/FTC with dolutegravir plus TAF/FTC or with single-pill dolutegravir/abacavir/lamivudine (Triumeq) in antiretroviral-naive people. These trials are no longer recruiting participants.
Mark Mascolini writes about HIV infection.
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