Bictegravir-Based Regimen Noninferior to Dolutegravir-Based Regimens for HIV Treatment

By Will Boggs MD

June 07, 2019

NEW YORK (Reuters Health) - A single-tablet regimen of bictegravir, emtricitabine and tenofovir alafenamide is noninferior to regimens of dolutegravir coformulated with emtricitabine and tenofovir alafenamide or with abacavir and lamivudine for the initial treatment of HIV-1 infection, according to results from two randomized phase 3 trials.

"The HIV regimens studied in these trials set a new standard for treatment of this infection, as about 90% of people treated with these medications achieved and maintained viral suppression, treatment-related discontinuations were rare, and no resistance to the antiretrovirals emerged," said Dr. David A. Wohl of the University of North Carolina at Chapel Hill.

"But with such potent, well-tolerated, and relatively resistant-to-resistance therapies for HIV infection, even somewhat modest differences between regimens can be important when selecting regimens that may be taken for many years," he told Reuters Health by email.

Bictegravir is a potent integrase strand-transfer inhibitor with a high in vitro barrier to resistance and in vitro activity against some variants that have reduced susceptibility to dolutegravir.

Dr. Wohl and colleagues present the key secondary week-96 results of two phase 3 trials comparing bictegravir-emtricitabine-tenofovir alafenamide versus dolutegravir-based regimens as initial treatment for people with HIV-1 infection.

In the first study, the bictegravir combination was noninferior to the dolutegravir-emtricitabine-tenofovir alafenamide combination in the U.S. Food and Drug Administration (FDA) snapshot analysis: 84% of the bictegravir group and 86% of the dolutegravir group had plasma HIV-1 RNA less than 50 copies per mL at week 96.

A modified snapshot analysis excluding participants without HIV-1 RNA results after baseline also showed noninferiority between the two treatment groups, the researchers report in The Lancet HIV, online May 5.

The two treatments were also associated with similar proportions of participants having HIV-1 RNA less than 20 copies per mL at week 96, but CD4 cell counts increased to a greater extent in the dolutegravir group (mean increase, 281 cells per uL) than in the bictegravir group (mean increase, 237 cells per uL).

In the second study, the bictegravir combination was noninferior to the dolutegravir-abacavir-lamivudine combination in the snapshot analysis: 88% of the bictegravir group and 90% of the dolutegravir group had plasma HIV-1 RNA less than 50 copies per mL at week 96.

CD4 cell counts increased to a similar extent from baseline to week 96 in the two treatment groups.

Significantly fewer participants in both studies had drug-related adverse events in the bictegravir group than in the dolutegravir group. No single adverse event met the 5% threshold for between-group statistical difference in the first study, whereas drug-related nausea was significantly more common with the dolutegravir regimen in the second study.

Changes from baseline in fasting lipid parameters were similar between groups at week 96 of the first study. In the second study, increases in fasting total cholesterol, LDL cholesterol, and total-to-HDL-cholesterol at week 96 were significantly higher in the bictegravir group.

No resistance developed to any component of either treatment regimen in either study.

"The trials demonstrate that each of the three regimens examined worked well, but there were some differences - mainly, for me, that abacavir caused more nausea than tenofovir alafenamide," Dr. Wohl said.

"That bictegravir is coformulated in a small single tablet with tenofovir alafenamide and emtricitabine is a plus - especially for those who are concerned about the short- or long-term complications of abacavir," he said. "Longer-term and real-world data on the two-drug regimen of dolutegravir and lamivudine will help us when evaluating this as an alternative to tenofovir alafenamide, bictegravir, and emtricitabine."

Dr. Tristan J. Barber from Royal Free London NHS Foundation Trust, who wrote an accompanying editorial, told Reuters Health by email, "What we have at the moment are two very different approaches - one being 3 drugs in a single pill, the other being 2-drug therapy based on dolutegravir. The studies tell us that the backbone drugs (tenofovir alafenamide (TAF) and abacavir) can cause issues, as well as the integrase inhibitors themselves having their own side effects."

"The choice will come down to some medical and patient factors, as well as patient and physician preference," he said. "What would be amazing to see is a naive study which put dolutegravir/lamivudine up against bictegravir/emtricitabine/TAF to really inform practice."

Gilead Sciences, Inc. funded both studies, employed several of the authors and had various relationships with others, including Dr. Wohl and Dr. Barber.

SOURCE: https://bit.ly/2VK7isp, https://bit.ly/30KMDIK and https://bit.ly/2JVM8W5

Lancet HIV 2019.

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