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Bictegravir Single-Dose Combo Found to Be As Safe & Effective As DTG/ABC/3TC

Week 48 safety results show that switching to B/F/TAF was noninferior to remaining on DTG/ABC/3TC.

The once-daily, single tablet HIV regimen that combines bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF), known commercially as Gilead’s Biktarvy, proved to be a hot topic at the 25th Conference on Retroviruses and Opportunistic Infections (CROI).

In a heavily attended oral abstract session, Jean-Michel Molina, MD, Hôpital Saint-Louis, in Paris, France, presented week 48 safety and efficacy data pertaining to switching from DTG/Abacavir/3TC (DTG/ABC/3TC) to B/F/TAF.

Recently approved by the US Food and Drug Administration (FDA), the Biktarvy regimen is indicated for the treatment of adults with HIV-1 who have no history of antiretroviral therapy (ART), or to replace a current ART regimen in those who have achieved virologic suppression.

“As you know, bictegravir is a novel, unboosted, potent integrase inhibitor with a high in vitro barrier to resistance and it has low potential for drug-drug interactions,” Dr. Molina said. “In large phase 3 trials, B/F/TAF was shown to be noninferior to dolutegravir (DTG)-containing regimens in treatment naïve patients and to boosted atazanivir (ATV) or darunivir (DRV)-containing regimens in virologically-suppressed patients.”

In all phase 3 trials, no treatment-emergent viral resistance to B/F/TAF was reported.

For the double-blind study, the investigators randomized HIV-suppressed adults on a regimen containing DTG/ABC/3TC who had an HIV RNA level that was below 50 copies/mL for at least 3 months with an eGFR below 50 mL per minute, no active HPV infection, no known resistance to study drugs to either switch to the single-dose B/F/TAF regimen or continue on their DTG/ABC/3TC regimen for the duration of 8 weeks.

Patients were enrolled in North America, Europe, and Australia. The median age of participants was 46 years and the majority of participants were white males. “The median CD4 cell count was quite high, with an average of over 700 for B/F/TAF compared with 661 for DTG/ABC/3TC,” noted Dr. Molina. “Also, the median eGFR was 101 mL/minute.”

The primary endpoint of the study was the proportion of patients with a viral load above or equal to 50 copies/mL at week 48. The results showed that at week 48, the proportion of patients with a viral load above 50 copies per mL was 1.1% with B/F/TAF and 0.4% with DTG/ABC/3TC. The treatment difference was 0.7% and the confidence interval (CI) crossed zero and remained within the 4% noninferiority margin, which demonstrated that B/F/TAF was noninferior to DTG/ABC/3TC in this study. Furthermore, the proportion of patients who remained fully suppressed at 48 weeks was high—94% with B/F/TAF and 95% with DTG/ABC/3TC.

Both treatment regimens were found to be well-tolerated by participants; only 2% of individuals in the B/F/TAF arm and 1% in the DTG/ABC/3TC arm discontinued the study drugs due to an adverse event. “If you look at the different adverse events, only headaches were reported in more than 1 individual: 2 in the B/F/TAF arm and 1 in the DTG/ABC/3TC arm,” shared Dr. Molina said. “When you look at the different adverse events, you don’t see any major differences across the 2 study arms.”

He noted that 2 individuals in the B/F/TAF arm died, but the causes were unrelated to the drugs involved in the study.

More grade 3 and 4 laboratory abnormalities were noted in the B/F/TAF arm compared with the DTG/ABC/3TC arm. “But this was driven mainly by a more frequent increase in amylase and ALT in the B/F/TAF arm,” Dr. Molina explained. “If you look at the 7 individuals who had the grade 3 or 4 amylase increase, you could see that 4 out of 7 had normal lipase. There were no cases of rhabdomyolysis, and all amylase elevations were actually transient.”

In terms of changes from baseline in eGFR, quantitative proteinuria, bone marrow density, and fasting lipids, there were only small changes from baseline in either arm, and no notable difference across the arms.

“When you think about switching regimens, you want to make sure that the new regimen is well-tolerated. Because oftentimes when people switch from 1 regimen to another, they usually experience a number of adverse events that might be related to the new drugs,” Dr. Molina shared in a press conference on the presentation. “What was remarkable about this study was that the tolerability was very similar; there was no increase in adverse events when [patients were] switched to the new single-tablet regimen.”

According to Dr. Molina, this adds another treatment option to choose from for clinicians and patients alike. The data yielded in the study can provide more information about available treatment options and can even eventually be extended for first-line treatment, or, of course, a switch.